DOCSLIB.ORG

Chemokine Ligand (CCL)20, and CCL21 This Information Is Current As of October 6, 2021

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemokine Ligand (CCL)20, and CCL21 This Information Is Current As of October 6, 2021 HIV Type 1 Glycoprotein 120 Inhibits Human B Cell Chemotaxis to CXC Chemokine Ligand (CXCL) 12, CC Chemokine Ligand (CCL)20, and CCL21 This information is current as of October 6, 2021. Gamal Badr, Gwenoline Borhis, Dominique Treton, Christiane Moog, Olivier Garraud and Yolande Richard J Immunol 2005; 175:302-310; ; doi: 10.4049/jimmunol.175.1.302 http://www.jimmunol.org/content/175/1/302 Downloaded from References This article cites 64 articles, 39 of which you can access for free at: http://www.jimmunol.org/content/175/1/302.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 6, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology HIV Type 1 Glycoprotein 120 Inhibits Human B Cell Chemotaxis to CXC Chemokine Ligand (CXCL) 12, CC Chemokine Ligand (CCL)20, and CCL211 Gamal Badr,* Gwenoline Borhis,* Dominique Treton,* Christiane Moog,† Olivier Garraud,‡ and Yolande Richard2* We analyzed the modulation of human B cell chemotaxis by the gp120 proteins of various HIV-1 strains. X4 and X4/R5 gp120 inhibited B cell chemotaxis toward CXCL12, CCL20, and CCL21 by 40–50%, whereas R5 gp120 decreased inhibition by 20%. This gp120-induced inhibition was strictly dependent on CXCR4 or CCR5 and lipid rafts but not on CD4 or VH3-expressing BCR. Inhibition did not impair the expression or ligand-induced internalization of CCR6 and CCR7. Our data suggest that gp120/ CXCR4 and gp120/CCR5 interactions lead to the cross-desensitization of CCR6 and CCR7 because gp120 does not bind CCR6 ␤ and CCR7. Unlike CXCL12, gp120 did not induce the activation of phospholipase C 3 and PI3K downstream from CXCR4, Downloaded from whereas p38 MAPK activation was observed. Similar results were obtained if gp120-treated cells were triggered by CCL21 and CCL20. Our results are consistent with a blockade restricted to signaling pathways using phosphatidylinositol-4,5-bisphosphate as a substrate. X4 and X4/R5 gp120 induced the cleavage of CD62 ligand by a mechanism dependent on matrix metalloproteinase ␣ 1 and 3, CD4, CXCR4, G i, and p38 MAPK, whereas R5 gp120 did not. X4 and X4/R5 gp120 also induced the relocalization of cytoplasmic CD95 to the membrane and a 23% increase in CD95-mediated apoptosis. No such effects were observed with R5 gp120. The gp120-induced decrease in B cell chemotaxis and CD62 ligand expression, and increase in CD95-mediated B cell http://www.jimmunol.org/ apoptosis probably have major deleterious effects on B cell responsiveness during HIV infection and in vaccination trials. The Journal of Immunology, 2005, 175: 302–310. uman immunodeficiency virus-1 infection is associated a superantigen to conserved VH3 framework regions, activating with strong polyclonal B cell activation, increasing the and depleting these cells (17, 18). As VH3 genes are the key de- H percentage of activated B cells in the periphery (1–5), terminants of Abs specific for bacterial polysaccharide Ags, the and with strong, sustained follicular hyperplasia in secondary lym- depletion of VH3-expressing B cells may contribute to the observed phoid organs during the asymptomatic phase of the disease (6–8). increase in the incidence of secondary infections in HIV-infected pa- The B cells of HIV-infected patients spontaneously secrete Ig but tients (19). Scamurra et al. (10) recently showed in vivo that the de- by guest on October 6, 2021 are unable to mount a T cell-dependent B cell response (1, 9, 10). pletion of peripheral VH3-expressing memory B cells, but not of naive Antiretroviral therapy decreases HIV-1-driven B cell hyperactiv- B cells, in HIV-infected patients involves gp120 binding. ity, polyclonal B cell activation, and Ig production in patients (11). Lymphocyte recirculation, which is critical for effective immu- These findings strongly suggest that the sustained replication of nity, is tightly regulated by the expression of adhesion molecules HIV-1 affects differentiation in lymphoid tissue. The mechanisms and chemoattractant receptors on lymphocytes, combined with the by which HIV-1 impairs the humoral response may result from spatial and temporal expression of ligands for these receptors by a intrinsic B cell defects or dysfunctional dialogue between T and B variety of tissue cells (20–23). Human B cells express several cells. Soluble Tat and gp120, biologically active extracellular pro- chemokine receptors, including CXCR4, CXCR5, CCR6, and teins released by HIV-1-infected cells, induce intrinsic defects in CCR7, and respond to their cognate ligands CXCL12, CXCL13, human B cells (12–15). We previously showed that Tat selectively CCL20, and CCL21 and CCL19, respectively. Triggering of the inhibits the BCR-mediated proliferation of naive and memory B BCR, CD40 and the IL-4R modulates chemokine receptor expres- cells, and the production of cytokines and Ig. In contrast, Tat dou- sion and chemotaxis in B cells (24–26). Chemokines can bind to 3 ␣ bles the germinal center cell proliferation induced by CD40 mAb various pertussis toxin (PTX) -sensitive (G i) and PTX-insensi- ␣ ␣ ␣ plus IL-4 (16). The HIV-1 envelope protein gp120 may bind like tive (G q and G 15/16)G proteins, but chemotaxis is only ob- ␣ served upon activation of G i protein-coupled receptors (22). There is strong evidence that G␤␥, rather than G␣ subunits initiate *Institut National de la Sante´et de la Recherche Medicale, Unite´131, Institut Paris- i Sud sur les Cytokines, Clamart, France; †Universite´ Louis Pasteur, Strasbourg, the chemotactic response (27). We recently showed that human B France; and ‡Groupe Immunite´ des Muqueuses et Agents Pathoge`nes, Faculte´de cell chemotaxis to CXCL12, CXCL13, CCL21, and CCL20 de- Me´decine, Universite´Jean Monnet, Saint-Etienne, France pends on PI3K, phospholipase C (PLC)␤3, protein kinase C Received for publication November 1, 2004. Accepted for publication April 20, 2005. (PKC), RhoA, and NF-␬B. Although activated by chemokine re- The costs of publication of this article were defrayed in part by the payment of page ceptor-ligand interactions, neither p38 MAPK nor ERK1/2 are in- charges. This article must therefore be hereby marked advertisement in accordance ␤␥ with 18 U.S.C. Section 1734 solely to indicate this fact. volved in B cell chemotaxis (28). G stimulation also activates G 1 This work was supported by grants from the Institut National de la Sante´etdela Recherche Me´dicale, Universite´Paris-Sud, and Sidaction. 2 Address correspondence and reprint requests to Dr. Yolande Richard, Institut 3 Abbreviations used in this paper: PTX, pertussis toxin; PLC, phospholipase C; PKC, National de la Sante´et de la Recherche Me´dicale, Unite´131, Universite´Paris- protein kinase C; MFI, mean fluorescence intensity; CD62L, L-selectin; MARCKS, myr- Sud, 32 rue des Carnets, 92 140 Clamart, France. E-mail address: yolande.richard istoylated alanine-rich C kinase substrate; M␤CD, methyl-␤-cyclodextrin; MMP, matrix @ipsc.u-psud.fr metalloproteinase; PIP2, phosphatidylinositol-4,5-bisphosphate. Copyright © 2005 by The American Association of Immunologists, Inc. 0022-1767/05/$02.00 The Journal of Immunology 303 protein-coupled receptor kinases, which phosphorylate chemokine For in vitro culture assays, B cells (2 ϫ 106 cells/ml) were cultured in receptors, inducing their binding to ␤-arrestin (29) and their rapid RPMI 1640 (Invitrogen SARL) supplemented with 10 mM HEPES, 2 mM ␮ internalization (30). L-glutamine, 100 U/ml penicillin, 100 g/ml streptomycin, 1 mM sodium pyruvate, and 10% heat-inactivated FCS (complete medium) for 2 h, with We analyzed the effect of recombinant CXCR4-binding (X4), or without recombinant 10 nM gp120 (unless otherwise indicated). Pre- CCR5-binding (R5), or dual-binding (X4/R5) gp120 on the che- liminary experiments showed that B cell chemotaxis was maximally in- motactic response of human primary B cells. We found that gp120 hibited after2hofincubation with 10 nM gp120 from the various HIV-1 strongly inhibited the chemotactic response to CCL20 and CCL21, strains (data not shown). without inducing spontaneous apoptosis or impairing the expres- Flow cytometry sion and ligand-induced internalization of CCR6 and CCR7. B cell chemotaxis was inhibited more strongly by X4 and X4/R5 gp120 Chemokine receptor expression was analyzed by flow cytometry, using than by R5 gp120, consistent with CXCR4 being the more strongly PE-conjugated anti-CCR6 (clone 53103.111, IgG2b), anti-CCR5 (clone 45531.111, IgG2b), anti-CCR7 (clone 150503, IgG2a), and anti-CXCR4 expressed of these two receptors. The use of Abs blocking (clone 44717.111, IgG2b) mAbs from R&D Systems. PE-conjugated CD19 CXCR4, CCR5, or gp120 totally prevented the gp120-induced in- (IgG1) and CD95 (IgG1) mAbs and FITC- and PE-conjugated mouse iso- hibition of B cell chemotaxis whereas soluble CD4 slightly in- type-matched control IgG were purchased from BD Biosciences. FITC- creased it. In contrast to what was observed with CXCL12, we conjugated CD62L (clone FMC46, IgG2a) was purchased from Diaclone. To detect cytoplasmic CD95 expression, we treated B cells with the Cyto- found that X4 or X4/R5 gp120 did not activate the CXCR4- fix/Cytoperm kit (BD Biosciences) before staining with PE-conjugated dependent phosphorylation of PLC␤3, PI3K/AKT, ERK1/2, and CD95 mAb or mouse IgG1.
Load more

Recommended publications
  • Mice in Inflammation Psoriasiform Skin IL-22 Is Required for Imiquimod-Induced
    IL-22 Is Required for Imiquimod-Induced Psoriasiform Skin Inflammation in Mice Astrid B. Van Belle, Magali de Heusch, Muriel M. Lemaire, Emilie Hendrickx, Guy Warnier, Kyri This information is current as Dunussi-Joannopoulos, Lynette A. Fouser, Jean-Christophe of September 29, 2021. Renauld and Laure Dumoutier J Immunol published online 30 November 2011 http://www.jimmunol.org/content/early/2011/11/30/jimmun ol.1102224 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 29, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 30, 2011, doi:10.4049/jimmunol.1102224 The Journal of Immunology IL-22 Is Required for Imiquimod-Induced Psoriasiform Skin Inflammation in Mice Astrid B. Van Belle,*,† Magali de Heusch,*,† Muriel M. Lemaire,*,† Emilie Hendrickx,*,† Guy Warnier,*,† Kyri Dunussi-Joannopoulos,‡ Lynette A. Fouser,‡ Jean-Christophe Renauld,*,†,1 and Laure Dumoutier*,†,1 Psoriasis is a common chronic autoimmune skin disease of unknown cause that involves dysregulated interplay between immune cells and keratinocytes.
    [Show full text]
  • Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1
    pathogens Article Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1 Acacia F. Dishman 1,2,†, Jie He 3,†, Brian F. Volkman 1,* and Anna R. Huppler 3,* 1 Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] 2 Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA 3 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] * Correspondence: [email protected] (B.F.V.); [email protected] (A.R.H.) † These authors contributed equally. Abstract: Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α–β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills C. albicans but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and Candida killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill Candida, but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate Citation: Dishman, A.F.; He, J.; the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associ- Volkman, B.F.; Huppler, A.R.
    [Show full text]
  • CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice
    ORIGINAL ARTICLE JBMR CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice Michele Doucet, Swaathi Jayaraman, Emily Swenson, Brittany Tusing, Kristy L Weber,Ã and Scott L Kominsky Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA ABSTRACT CCL20 is a member of the macrophage inflammatory protein family and is reported to signal monogamously through the receptor CCR6. Although studies have identified the genomic locations of both Ccl20 and Ccr6 as regions important for bone quality, the role of CCL20/CCR6 signaling in regulating bone mass is unknown. By micro–computed tomography (mCT) and histomorphometric analysis, we show that global loss of Ccr6 in mice significantly decreases trabecular bone mass coincident with reduced osteoblast numbers. Notably, CCL20 and CCR6 were co-expressed in osteoblast progenitors and levels increased during osteoblast differentiation, indicating the potential of CCL20/CCR6 signaling to influence osteoblasts through both autocrine and paracrine actions. With respect to autocrine effects, CCR6 was found to act as a functional G protein–coupled receptor in osteoblasts and although its loss did not appear to affect the number or proliferation rate of osteoblast progenitors, differentiation was significantly inhibited as evidenced by delays in osteoblast marker gene expression, alkaline phosphatase activity, and mineralization. In addition, CCL20 promoted osteoblast survival concordant with activation of the PI3K-AKT pathway. Beyond these potential autocrine effects, osteoblast-derived CCL20 stimulated the recruitment of macrophages and T cells, known facilitators of osteoblast differentiation and survival. Finally, we generated mice harboring a global deletion of Ccl20 and found that Ccl20-/- mice exhibit a reduction in bone mass similar to that observed in Ccr6-/- mice, confirming that this phenomenon is regulated by CCL20 rather than alternate CCR6 ligands.
    [Show full text]
  • Establishment of HIV-1 Latency in Resting CD4+ T Cells Depends on Chemokine-Induced Changes in the Actin Cytoskeleton
    Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton Paul U. Camerona,b,c,1, Suha Salehb,1, Georgina Sallmannb, Ajantha Solomonb, Fiona Wightmanb, Vanessa A. Evansb, Genevieve Boucherd, Elias K. Haddadd,Rafick-Pierre Sekalyd, Andrew N. Harmane, Jenny L. Andersonf, Kate L. Jonesf, Johnson Makf,g, Anthony L. Cunninghame, Anthony Jaworowskib,c,f, and Sharon R. Lewina,b,f,2 aInfectious Diseases Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia; Departments of bMedicine and cImmunology, Monash University, Melbourne 3004, Australia; dLaboratoire d’Immunologie, Centre de Recherche de Centre Hospitalier de L’Universitie de Montreal, Saint-Luc, Quebec, Canada; eWestmead Millenium Research Institute, Westmead 2145, Australia; fCentre for Virology, Burnet Institute, Melbourne 3004, Australia; and gDepartment of Biochemistry and Molecular Biology, Department of Microbiology, Monash University, Clayton 3800, Australia Edited by Malcolm A. Martin, National Institute of Allergy and Infectious Diseases, Bethesda, MD, and approved August 23, 2010 (received for review March 8, 2010) Eradication of HIV-1 with highly active antiretroviral therapy mokines, in addition to CXCR4 ligands may facilitate HIV-1 + (HAART) is not possible due to the persistence of long-lived, entry and integration in resting CD4 T cells and that this was latently infected resting memory CD4+ T cells. We now show that mediated via activation of actin. + HIV-1 latency can be established in resting CD4+ T cells infected We now show that the exposure of resting CD4 T cells to with HIV-1 after exposure to ligands for CCR7 (CCL19), CXCR3 the chemokines CCL19, CXCL10, and CCL20, all of which fi (CXCL9 and CXCL10), and CCR6 (CCL20) but not in unactivated regulate T-cell migration, allows for ef cient HIV-1 nuclear lo- + calization and integration of the HIV-1 provirus, that this oc- CD4 T cells.
    [Show full text]
  • A Role for the Pattern Recognition Receptor Nod2 in Promoting Recruitment of CD103&Plus; Dendritic Cells to the Colon In
    ARTICLES nature publishing group A role for the pattern recognition receptor Nod2 in promoting recruitment of CD103 þ dendritic cells to the colon in response to Trichuris muris infection R Bowcutt1,4, M Bramhall1, L Logunova1, J Wilson2, C Booth2, SR Carding3, R Grencis1 and S Cruickshank1 The ability of the colon to generate an immune response to pathogens, such as the model pathogen Trichuris muris,isa fundamental and critical defense mechanism. Resistance to T. muris infection is associated with the rapid recruitment of dendritic cells (DCs) to the colonic epithelium via epithelial chemokine production. However, the epithelial–pathogen interactions that drive chemokine production are not known. We addressed the role of the cytosolic pattern recognition receptor Nod2. In response to infection, there was a rapid influx of CD103 þ CD11c þ DCs into the colonic epithelium in wild-type (WT) mice, whereas this was absent in Nod2 À / À animals. In vitro chemotaxis assays and in vivo experiments using bone marrow chimeras of WT mice reconstituted with Nod2 À / À bone marrow and infected with T. muris demonstrated that the migratory function of Nod2 À / À DCs was normal. Investigation of colonic epithelial cell (CEC) innate responses revealed a significant reduction in epithelial production of the chemokines CCL2 and CCL5 but not CCL20 by Nod2-deficient CECs. Collectively, these data demonstrate the importance of Nod2 in CEC responses to infection and the requirement for functional Nod2 in initiating host epithelial chemokine-mediated responses and subsequent DC recruitment and T-cell responses following infection. INTRODUCTION characterized, how and why these immune responses are The gastrointestinal-dwelling parasite, Trichuris muris initiated is still unclear.
    [Show full text]
  • Protein Engineering of the Chemokine CCL20 Prevents Psoriasiform Dermatitis in an IL-23–Dependent Murine Model
    Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23–dependent murine model A. E. Getschmana, Y. Imaib,c, O. Larsend, F. C. Petersona,X.Wub,e, M. M. Rosenkilded, S. T. Hwangb,e, and B. F. Volkmana,1 aDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226; bDepartment of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226; cDepartment of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; dLaboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; and eDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA 95816 Edited by Jason G. Cyster, University of California, San Francisco, CA, and approved October 10, 2017 (received for review April 4, 2017) Psoriasis is a chronic inflammatory skin disease characterized by the combination of intracellular responses, including activation of infiltration of T cell and other immune cells to the skin in response to heterotrimeric G proteins and β-arrestin–mediated signal trans- injury or autoantigens. Conventional, as well as unconventional, γδ duction that culminate in directional cell migration. Inhibition of T cells are recruited to the dermis and epidermis by CCL20 and other chemokine signaling by small molecule or peptide antagonists chemokines. Together with its receptor CCR6, CCL20 plays a critical typically blocks GPCR signaling by binding the orthosteric site and role in the development of psoriasiform dermatitis in mouse models. preventing activation by the chemokine agonist (13, 14). However, We screened a panel of CCL20 variants designed to form dimers sta- partial or biased agonists of chemokine receptors, which are bilized by intermolecular disulfide bonds.
    [Show full text]
  • Airway Epithelial Cells Release MIP-3 /CCL20 in Response to Cytokines and Ambient Particulate Matter
    Airway Epithelial Cells Release MIP-3␣/CCL20 in Response to Cytokines and Ambient Particulate Matter Joan Reibman, Yanshen Hsu, Lung Chi Chen, Bertram Bleck, and Terry Gordon Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Department of Environmental Medicine, Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York The initiation and maintenance of airway immune responses text of MHC Class II peptide complexes and, in the presence in Th2 type allergic diseases such as asthma are dependent on of costimulatory molecules and in the appropriate cytokine the specific activation of local airway dendritic cells (DCs). The microenvironment, induce a polarized T-cell response (1–4). cytokine microenvironment, produced by local cells, influences DCs may present antigen in such a way as to induce a Th1 the recruitment of specific subsets of immature DCs and their or Th2 response (4). The polarization of DCs is believed subsequent maturation. In the airway, DCs reside in close prox- imity to airway epithelial cells (AECs). We examined the ability to be determined by the cytokine microenvironment at the of primary culture human bronchial epithelial cells (HBECs) to site of DC maturation. In the airway, this microenvironment synthesize and secrete the recently described CC-chemokine, is induced in part by the airway epithelial cell (AEC). The MIP-3␣/CCL20. MIP-3␣/CCL20 is the unique chemokine ligand recruitment of immature DCs to the airway and the site of for CCR6, a receptor with a restricted distribution. MIP-3␣/ antigen exposure is tightly regulated and is dependent on CCL20 induces selective migration of DCs because CCR6 is ex- the release of select chemokines and the expression of spe- pressed on some immature DCs but not on CD14؉ DC precursors cific chemokine receptors by DCs (5).
    [Show full text]
  • Baseline CXCL10 and CXCL13 Levels Are Predictive Biomarkers for Tumor Necrosis Factor Inhibitor Therapy in Patients with Moderat
    Han et al. Arthritis Research & Therapy (2016) 18:93 DOI 10.1186/s13075-016-0995-0 RESEARCH ARTICLE Open Access Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: a pilot, prospective study Bobby Kwanghoon Han1*, Igor Kuzin2, John P. Gaughan3, Nancy J. Olsen4 and Andrea Bottaro2 Abstract Background: TNF inhibitors have been used as a treatment for moderate to severe RA patients. However, reliable biomarkers that predict therapeutic response to TNF inhibitors are lacking. In this study, we investigated whether chemokines may represent useful biomarkers to predict the response to TNF inhibitor therapy in RA. Methods: RA patients (n = 29) who were initiating adalimumab or etanercept were recruited from the rheumatology clinics at Cooper University Hospital. RA patients were evaluated at baseline and 14 weeks after TNF inhibitor therapy, and serum levels of CXCL10, CXCL13, and CCL20 were measured by ELISA. Responders (n = 16) were defined as patients who had good or moderate response at week 14 by EULAR response criteria, and nonresponders (n = 13) were defined as having no response. Results: Responders had higher levels of baseline CXCL10 and CXCL13 compared to nonresponders (p =0.03 and 0.002 respectively). There was no difference in CCL20 levels. CXCL10 and CXCL13 were highly correlated with each other, and were higher in seropositive RA patients. CXCL10 and CXCL13 levels were decreased after TNF inhibitor therapy in responders. Baseline additive levels of CXCL10 + 13 were correlated with changes in DAS score at 14 weeks after TNF inhibitor therapy (r = 0.42, p = 0.03), and ROC curve analyses for predictive ability of CXCL10 + 13 showed an AUC of 0.83.
    [Show full text]
  • Profiling of Healthy and Asthmatic Airway Smooth Muscle Cells Following IL-1Β Treatment: a Novel Role for CCL20 in Chronic Mucus Hyper-Secretion
    ERJ Express. Published on June 25, 2018 as doi: 10.1183/13993003.00310-2018 Early View Original article Profiling of healthy and asthmatic airway smooth muscle cells following IL-1β treatment: a novel role for CCL20 in chronic mucus hyper-secretion Alen Faiz, Markus Weckmann, Haitatip Tasena, Corneel J. Vermeulen, Maarten Van den Berge, Nick H.T. ten Hacken, Andrew J. Halayko, Jeremy P.T. Ward, Tak H. Lee, Gavin Tjin, Judith L. Black, Mehra Haghi, Cheng-Jian Xu, Gregory G. King, Claude S. Farah, Brian G. Oliver, Irene H. Heijink, Janette K. Burgess Please cite this article as: Faiz A, Weckmann M, Tasena H, et al. Profiling of healthy and asthmatic airway smooth muscle cells following IL-1β treatment: a novel role for CCL20 in chronic mucus hyper-secretion. Eur Respir J 2018; in press (https://doi.org/10.1183/13993003.00310-2018). This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Copyright ©ERS 2018 Copyright 2018 by the European Respiratory Society. Profiling of healthy and asthmatic airway smooth muscle cells following IL-1β treatment: a novel role for CCL20 in chronic mucus hyper-secretion Alen Faiz1,2,3,4, 5*, Markus Weckmann1,6, Haitatip Tasena3,4,5, Corneel. J.Vermeulen3,4, Maarten Van den Berge3,4, Nick .H.T. ten Hacken3, Andrew J.
    [Show full text]
  • Interleukin-22: a Potential Therapeutic Target in Atherosclerosis
    Luo et al. Mol Med (2021) 27:88 https://doi.org/10.1186/s10020-021-00353-9 Molecular Medicine REVIEW Open Access Interleukin-22: a potential therapeutic target in atherosclerosis Jin‑Wen Luo1, Yuan Hu2 , Jian Liu1, Huan Yang3* and Peng Huang1* Abstract Background: Atherosclerosis is recognized as a chronic immuno‑infammatory disease that is characterized by the accumulation of immune cells and lipids in the vascular wall. In this review, we focus on the latest advance regarding the regulation and signaling pathways of IL‑22 and highlight its impacts on atherosclerosis. Main body: IL‑22, an important member of the IL‑10 family of cytokines, is released by cells of the adaptive and innate immune system and plays a key role in the development of infammatory diseases. The binding of IL‑22 to its receptor complex can trigger a diverse array of downstream signaling pathways, in particular the JAK/STAT, to induce the expression of chemokines and proinfammatory cytokines. Recently, numerous studies suggest that IL‑22 is involved in the pathogenesis of atherosclerosis by regulation of VSMC proliferation and migration, angiogenesis, infammatory response, hypertension, and cholesterol metabolism. Conclusion: IL‑22 promotes the development of atherosclerosis by multiple mechanisms, which may be a promising therapeutic target in the pathogenesis of atherosclerosis. Keywords: Atherosclerosis, IL‑22, Infammatory response, Cytokine, Cholesterol metabolism Introduction angiogenesis, hypertension, vascular smooth muscle cell Cardiovascular diseases (CVDs) represent the major (VSMC), and cholesterol metabolism. factor of disability and premature death worldwide. Interleukin-22 (IL-22), discovered in 2000, is known as Recently, the World Health Organization (WHO) a crucial member of the IL-10 cytokine family (Dumout- revealed that CVD accounts for > 17 million deaths per ier et al.
    [Show full text]
  • Explorations Into Host Defense Against Plasmodium Falciparum: Mechanistic and Structure-Function Studies of Antimalarial Chemokines
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2014 Explorations into host defense against Plasmodium falciparum: mechanistic and structure-function studies of antimalarial chemokines Melissa Suzanne Love University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biochemistry Commons, Parasitology Commons, and the Pharmacology Commons Recommended Citation Love, Melissa Suzanne, "Explorations into host defense against Plasmodium falciparum: mechanistic and structure-function studies of antimalarial chemokines" (2014). Publicly Accessible Penn Dissertations. 1352. https://repository.upenn.edu/edissertations/1352 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1352 For more information, please contact [email protected]. Explorations into host defense against Plasmodium falciparum: mechanistic and structure-function studies of antimalarial chemokines Abstract Antimicrobial peptides (AMPs) are small (2-8kDa) peptides that have remained an important part of innate immunity over evolutionary time. AMPs vary greatly in sequence and structure, but display broad- spectrum activity against bacteria, yeast, and fungi via direct perturbation of the pathogen membrane. AMPs are typically amphipathic, and contain 2-4 positively charged amino acid residues. It has been previously shown that many chemokines also display AMP activity, both via their canonical function recruiting immune cells to the site of an infection and by direct interaction with the pathogen itself. Many antimicrobial chemokines have the same tertiary structure: an N-terminal loop responsible for receptor recognition; a three-stranded antiparallel β-sheet domain that provides a stable scaffold; and a C-terminal α-helix that folds over the β-sheet and helps to stabilize the overall structure.
    [Show full text]
  • Review Article Sarcoidosis: Immunopathogenesis and Immunological Markers
    Hindawi Publishing Corporation International Journal of Chronic Diseases Volume 2013, Article ID 928601, 13 pages http://dx.doi.org/10.1155/2013/928601 Review Article Sarcoidosis: Immunopathogenesis and Immunological Markers Wei Sheng Joshua Loke,1,2 Cristan Herbert,1 and Paul S. Thomas1,2 1 Inflammation and Infection Research Centre, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia 2 Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW 2031, Australia Correspondence should be addressed to Paul S. Thomas; [email protected] Received 20 April 2013; Accepted 17 June 2013 Academic Editor: Maria Gazouli Copyright © 2013 Wei Sheng Joshua Loke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis.
    [Show full text]