Serpins—From Trap to Treatment
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Serpinb1 Controls Encephalitogenic T Helper Cells in Neuroinflammation
SerpinB1 controls encephalitogenic T helper cells in neuroinflammation Lifei Houa,b,1,2, Deepak A. Raoc,d, Koichi Yukie,f, Jessica Cooleya, Lauren A. Hendersonb,g, A. Helena Jonssonc,d, Dion Kaisermanh, Mark P. Gormanb,i, Peter A. Nigrovicc,d,g, Phillip I. Birdh, Burkhard Becherj, and Eileen Remold-O’Donnella,b,k,2 aThe Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115; bDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115; cDivision of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115; dDepartment of Medicine, Harvard Medical School, Boston, MA 02115; eDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115; fDepartment of Anesthesiology, Harvard Medical School, Boston, MA 02115; gDivision of Immunology, Boston Children’s Hospital, Boston, MA 02115; hDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia; iDepartment of Neurology, Boston Children’s Hospital, Boston, MA 02115; jInflammation Unit, Institute of Experimental Immunology, University of Zurich, CH-8057 Zurich, Switzerland; and kDepartment of Hematology/Oncology, Harvard Medical School, Boston, MA 02115 Edited by Jean Laurent-Casanova, Rockefeller University, New York, NY, and approved August 27, 2019 (received for review April 5, 2019) SerpinB1, a protease inhibitor and neutrophil survival factor, was flammatory tissue injury and neutrophil death, and in naïve mice, recently linked with IL-17–expressing T cells. Here, we show that preserves the bone marrow reserve of mature neutrophils by serpinB1 (Sb1) is dramatically inducedinasubsetofeffector restricting spontaneous cell death mediated by the granule serine CD4 cells in experimental autoimmune encephalomyelitis (EAE). -
ONCOGENOMICS Through the Use of Chemotherapeutic Agents
Oncogene (2002) 21, 7749 – 7763 ª 2002 Nature Publishing Group All rights reserved 0950 – 9232/02 $25.00 www.nature.com/onc Expression profiling of primary non-small cell lung cancer for target identification Jim Heighway*,1, Teresa Knapp1, Lenetta Boyce1, Shelley Brennand1, John K Field1, Daniel C Betticher2, Daniel Ratschiller2, Mathias Gugger2, Michael Donovan3, Amy Lasek3 and Paula Rickert*,3 1Target Identification Group, Roy Castle International Centre for Lung Cancer Research, University of Liverpool, 200 London Road, Liverpool L3 9TA, UK; 2Institute of Medical Oncology, University of Bern, 3010 Bern, Switzerland; 3Incyte Genomics Inc., 3160 Porter Drive, Palo Alto, California, CA 94304, USA Using a panel of cDNA microarrays comprising 47 650 Introduction transcript elements, we have carried out a dual-channel analysis of gene expression in 39 resected primary The lack of generally effective therapies for lung cancer human non-small cell lung tumours versus normal lung leads to the high mortality rate associated with this tissue. Whilst *11 000 elements were scored as common disease. Recorded 5-year survival figures vary, differentially expressed at least twofold in at least one to some extent perhaps reflecting differences in sample, 96 transcripts were scored as over-represented ascertainment methods, but across Europe are approxi- fourfold or more in at least seven out of 39 tumours mately 10% (Bray et al., 2002). Whilst surgery is an and 30 sequences 16-fold in at least two out of 39 effective strategy for the treatment of localized lesions, tumours, including 24 transcripts in common. Tran- most patients present with overtly or covertly dissemi- scripts (178) were found under-represented fourfold in nated disease. -
Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children
Edinburgh Research Explorer Polygenic risk score of SERPINA6/SERPINA1 associates with diurnal and stress-induced HPA axis activity in children Citation for published version: Utge, S, Räikkönen, K, Kajantie, E, Lipsanen, J, Andersson, S, Strandberg, T, Reynolds, R, Eriksson, JG & Lahti, J 2018, 'Polygenic risk score of SERPINA6/SERPINA1 associates with diurnal and stress-induced HPA axis activity in children', Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2018.04.009 Digital Object Identifier (DOI): 10.1016/j.psyneuen.2018.04.009 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Psychoneuroendocrinology General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 29. Sep. 2021 Psychoneuroendocrinology 93 (2018) 1–7 Contents lists available at ScienceDirect Psychoneuroendocrinology journal homepage: www.elsevier.com/locate/psyneuen Polygenic risk score of SERPINA6/SERPINA1 associates with diurnal and T stress-induced HPA axis activity in children Siddheshwar Utgea,b, Katri Räikkönena, Eero Kajantiec,d,e, Jari Lipsanena, Sture Anderssond, ⁎ Timo Strandbergf,g, Rebecca M. -
Biomarkers of Neonatal Skin Barrier Adaptation Reveal Substantial Differences Compared to Adult Skin
www.nature.com/pr CLINICAL RESEARCH ARTICLE OPEN Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin Marty O. Visscher1,2, Andrew N. Carr3, Jason Winget3, Thomas Huggins3, Charles C. Bascom3, Robert Isfort3, Karen Lammers1 and Vivek Narendran1 BACKGROUND: The objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2). METHODS: Skin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34–<37 weeks (LPT), and ≥37 weeks (FT). RESULTS: Forty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2. CONCLUSIONS: Neonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the 1234567890();,: barrier antimicrobial properties. -
Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo -
A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REPORT A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss Aslı Sırmacı,1,2 Seyra Erbek,3 Justin Price,1,2 Mingqian Huang,4 Duygu Duman,5 F. Basxak Cengiz,5 Gu¨ney Bademci,1,2 Suna Tokgo¨z-Yılmaz,5 Burcu Hisxmi,5 Hilal O¨ zdag˘,6 Banu O¨ ztu¨rk,7 Sevsen Kulaksızog˘lu,8 Erkan Yıldırım,9 Haris Kokotas,10 Maria Grigoriadou,10 Michael B. Petersen,10 Hashem Shahin,11 Moien Kanaan,11 Mary-Claire King,12 Zheng-Yi Chen,4 Susan H. Blanton,1,2 Xue Z. Liu,2,13 Stephan Zuchner,1,2 Nejat Akar,5 and Mustafa Tekin1,2,* More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromo- some 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DFNB91 and encodes for an intra- cellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. -
Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors
RESEARCH ARTICLE Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors Jeroen F. Vermeulen1, Wim van Hecke1, Wim G. M. Spliet1, José Villacorta Hidalgo3, Paul Fisch3, Roel Broekhuizen1, Niels Bovenschen1,2* 1 Department of Pathology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands, 2 Laboratory of Translational Immunology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands, 3 Institute of Pathology, University Medical Center Freiburg, 79106, Freiburg, Germany * [email protected] Abstract Background OPEN ACCESS Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant Citation: Vermeulen JF, van Hecke W, Spliet WGM, primary brain tumors that occur in young infants. Using current standard therapy, up to 80% Villacorta Hidalgo J, Fisch P, Broekhuizen R, et al. of the children still dies from recurrent disease. Cellular immunotherapy might be key to (2016) Pediatric Primitive Neuroectodermal Tumors improve overall survival. To achieve efficient killing of tumor cells, however, immunotherapy of the Central Nervous System Differentially Express Granzyme Inhibitors. PLoS ONE 11(3): e0151465. has to overcome cancer-associated strategies to evade the cytotoxic immune response. doi:10.1371/journal.pone.0151465 Whether CNS-PNETs can evade the immune response remains unknown. Editor: Javier S Castresana, University of Navarra, SPAIN Methods Received: September 3, 2015 We examined by immunohistochemistry the immune response and immune evasion strate- Accepted: February 29, 2016 gies in pediatric CNS-PNETs. Published: March 10, 2016 Copyright: © 2016 Vermeulen et al. This is an open Results access article distributed under the terms of the Creative Commons Attribution License, which permits Here, we show that CD4+, CD8+, γδ-T-cells, and Tregs can infiltrate pediatric CNS-PNETs, unrestricted use, distribution, and reproduction in any although the activation status of cytotoxic cells is variable. -
Serpinb2 Is Involved in Cellular Response Upon UV Irradiation
www.nature.com/scientificreports OPEN SerpinB2 is involved in cellular response upon UV irradiation Hajnalka Majoros1, Zsuzsanna Ujfaludi1, Barbara Nikolett Borsos1, Viktória Vivien Hudacsek1, Zita Nagy3, Frederic Coin3, Krisztina Buzas2, Ilona Kovács4, Tamás Bíró5,6, Imre Miklós Boros1,2 1 Received: 20 August 2018 & Tibor Pankotai Accepted: 10 December 2018 Ultraviolet light induced pyrimidine dimer is a helix distortion DNA damage type, which recruits repair Published: xx xx xxxx complexes. However, proteins of these complexes that take part in both DNA damage recognition and repair have been well-described, the regulation of the downstream steps of nucleotide excision repair (NER) have not been clearly clarifed yet. In a high-throughput screen, we identifed SerpinB2 (SPB2) as one of the most dramatically upregulated gene in keratinocytes following UV irradiation. We found that both the mRNA and the protein levels of SPB2 were increased upon UV irradiation in various cell lines. Additionally, UV damage induced translocation of SPB2 from the cytoplasm to the nucleus as well as the damage induced foci formation of it. Here we show that SPB2 co-localizes with XPB involved in the NER pathway at UV-induced repair foci. Finally, we demonstrated that UV irradiation promoted the association of SPB2 with ubiquitylated proteins. In basal cell carcinoma tumour cells, we identifed changes in the subcellular localization of SPB2. Based on our results, we conclude that SPB2 protein has a novel role in UV-induced NER pathway, since it regulates the removal of the repair complex from the damaged site leading to cancerous malformation. Our genome is constantly exposed to endogenous and exogenous sources leading to DNA damage and impair- ment of genome integrity. -
Low P66shc with High Serpinb3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma
biology Article Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma Silvano Fasolato 1, Mariagrazia Ruvoletto 1 , Giorgia Nardo 2, Andrea Rasola 3, Marco Sciacovelli 3, Giacomo Zanus 4,5, Cristian Turato 6 , Santina Quarta 1 , Liliana Terrin 1, Gian Paolo Fadini 1 , Giulio Ceolotto 1, Maria Guido 1, Umberto Cillo 4,7, Stefano Indraccolo 2,4, Paolo Bernardi 3 and Patrizia Pontisso 1,* 1 Department of Medicine, University of Padua, Via Giustiniani, 2, 35128 Padua, Italy; [email protected] (S.F.); [email protected] (M.R.); [email protected] (S.Q.); [email protected] (L.T.); [email protected] (G.P.F.); [email protected] (G.C.); [email protected] (M.G.) 2 Istituto Oncologico Veneto IOV- IRCCS, 35128 Padua, Italy; [email protected] (G.N.); [email protected] (S.I.) 3 Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy; [email protected] (A.R.); [email protected] (M.S.); [email protected] (P.B.) 4 Department of Surgical, Oncological and Gastroenterological Sciences-DISCOG, University of Padua, 35128 Padua, Italy; [email protected] (G.Z.); [email protected] (U.C.); [email protected] (S.I) 5 Hepatobiliary and Pancreatic Surgery Unit-Treviso Hospital, 31100 Treviso, Italy 6 Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; [email protected] 7 Unit of Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, 35128 Padua, Italy * Correspondence: [email protected]; Tel.: +39-049-821-7872; Fax: +39-049-875-4179 Citation: Fasolato, S.; Ruvoletto, M.; Simple Summary: Cell proliferation and escape from apoptosis are important pathological features Nardo, G.; Rasola, A.; Sciacovelli, M.; of hepatocellular carcinoma, one of the tumors with the highest mortality rate worldwide. -
SERPINB3/4 Polyclonal Antibody
PRODUCT DATA SHEET Bioworld Technology,Inc. SERPINB3/4 polyclonal antibody Catalog: BS60990 Host: Rabbit Reactivity: Human,Mouse,Rat BackGround: Swiss-Prot: Metastasis of a primary tumor to a distant site is deter- P29508/P48594 mined through signaling cascades that break down inter- Purification&Purity: actions between the cell and extracellular matrix proteins. The antibody was affinity-purified from rabbit antiserum Among the proteins mediating metastasis are serine by affinity-chromatography using epitope-specific im- prote-ases, such as neutrophil elastase. In 1985, Dr. Jim munogen and the purity is > 95% (by SDS-PAGE). Travis and Dr. R.W. Carrell designated an emerging fam- Applications: ily of serine protease inhibitors as the serpin fam-ily, WB: 1:500~1:1000 which share homology in both primary amino acid se- Storage&Stability: quence and tertiary structure. Serpins contain a stretch of Store at 4°C short term. Aliquot and store at -20°C long peptide that mimics a true substrate for a corresponding term. Avoid freeze-thaw cycles. serine protease. Serine proteases bind to this substrate Specificity: mimic in a 1:1 stoichiometric fashion and become cata- SERPINB3/4 polyclonal antibody detects endogenous lytically inactive. Aberrant ex-pression of serpin family levels of SERPINB3/4 protein. members can contribute to a number of conditions, in- DATA: cluding emphysema (a-1 antitrypsin deficiency), fatal bleeding (elastase to thrombin specificity) and thrombosis (antithrombin deficiency), and are indicators of cancer stage phenotypes (circulating levels of squamous cell car- cinoma antigen, known as SCCA1, increase in advancing stages of some cervical, lung, esophageal and head and neck cancers). -
Differential Gene Expression of Serine Protease Inhibitors in Bovine
Hayashi et al. Reproductive Biology and Endocrinology 2011, 9:72 http://www.rbej.com/content/9/1/72 RESEARCH Open Access Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia Ken-Go Hayashi, Koichi Ushizawa, Misa Hosoe and Toru Takahashi* Abstract Background: SERPINs (serine protease inhibitors) regulate proteases involving fibrinolysis, coagulation, inflammation, cell mobility, cellular differentiation and apoptosis. This study aimed to investigate differentially expressed genes of members of the SERPIN superfamily between healthy and atretic follicles using a combination of microarray and quantitative real-time PCR (QPCR) analysis. In addition, we further determined mRNA and protein localization of identified SERPINs in estradiol (E2)-active and E2-inactive follicles by in situ hybridization and immunohistochemistry. Methods: We performed microarray analysis of healthy (10.7 +/- 0.7 mm) and atretic (7.8 +/- 0.2 mm) follicles using a custom-made bovine oligonucleotide microarray to screen differentially expressed genes encoding SERPIN superfamily members between groups. The expression profiles of six identified SERPIN genes were further confirmed by QPCR analysis. In addition, mRNA and protein localization of four SERPINs was investigated in E2- active and E2-inactive follicles using in situ hybridization and immunohistochemistry. Results: We have identified 11 SERPIN genes expressed in healthy and atretic follicles by microarray analysis. QPCR analysis confirmed that mRNA expression of four SERPINs (SERPINA5, SERPINB6, SERPINE2 and SERPINF2) was greater in healthy than in atretic follicles, while two SERPINs (SERPINE1 and SERPING1) had greater expression in atretic than in healthy follicles. In situ hybridization showed that SERPINA5, SERPINB6 and SERPINF2 mRNA were localized in GCs of E2-active follicles and weakly expressed in GCs of E2-inactive follicles. -
Characterisation of Serpinb2 As a Stress Response Modulator
University of Wollongong Research Online University of Wollongong Thesis Collection 1954-2016 University of Wollongong Thesis Collections 2015 Characterisation of SerpinB2 as a stress response modulator Jodi Anne Lee University of Wollongong Follow this and additional works at: https://ro.uow.edu.au/theses University of Wollongong Copyright Warning You may print or download ONE copy of this document for the purpose of your own research or study. The University does not authorise you to copy, communicate or otherwise make available electronically to any other person any copyright material contained on this site. You are reminded of the following: This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part of this work may be reproduced by any process, nor may any other exclusive right be exercised, without the permission of the author. Copyright owners are entitled to take legal action against persons who infringe their copyright. A reproduction of material that is protected by copyright may be a copyright infringement. A court may impose penalties and award damages in relation to offences and infringements relating to copyright material. Higher penalties may apply, and higher damages may be awarded, for offences and infringements involving the conversion of material into digital or electronic form. Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong. Recommended Citation Lee, Jodi Anne, Characterisation of SerpinB2 as a stress response modulator, Doctor of Philosophy thesis, School of Biological Sciences, University of Wollongong, 2015. https://ro.uow.edu.au/theses/4538 Research Online is the open access institutional repository for the University of Wollongong.