DOCSLIB.ORG

Predictive Value of Preoperative Serum CCL2, CCL18, and VEGF for the Patients with Gastric Cancer Jianghong Wu1,2†, Xiaowen Liu1,2† and Yanong Wang1,2*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Predictive Value of Preoperative Serum CCL2, CCL18, and VEGF for the Patients with Gastric Cancer Jianghong Wu1,2†, Xiaowen Liu1,2† and Yanong Wang1,2* Wu et al. BMC Clinical Pathology 2013, 13:15 http://www.biomedcentral.com/1472-6890/13/15 RESEARCH ARTICLE Open Access Predictive value of preoperative serum CCL2, CCL18, and VEGF for the patients with gastric cancer Jianghong Wu1,2†, Xiaowen Liu1,2† and Yanong Wang1,2* Abstract Background: To investigate the expression of chemokine ligand 2 (CCL2), chemokine ligand 18 (CCL18), and vascular endothelial growth factor (VEGF) in peripheral blood of patients with gastric cancer and their correlation with presence of malignancy and disease progression. Methods: Sixty patients with pathological proved gastric cancer were prospectively included into study. The levels of CCL2, CCL18, and VEGF in peripheral blood were examined by enzyme-linked immunosorbentassay (ELISA). Peripheral blood from 20 healthy people was examined as control. Results: The preoperative serum levels of CCL2, CCL18 and VEGF in gastric cancer patients were significantly higher than that of controls (P <0.001, P <0.001, and P <0.001, respectively). ROC curve analysis showed that with a cut-off value of ≥1272.8, the VEGF*CCL2 predicted the presence of gastric cancer with 83% sensitivity and 80% specificity. Preoperative serum CCL2 was significantly correlated to N stage (P =0.040); CCL18 associated with N stage (P =0.002), and TNM stage (P =0.002); VEGF correlated to T stage (P =0.000), N stage (P =0.015), and TNM stage (P =0.000). Conclusion: Preoperative serum levels of CCL2 and VEGF could play a crucial role in predicting the presence and progression of gastric cancer. Keywords: Gastric cancer, Diagnosis, Biological markers Background Chemokines were a kind of low-molecular weight cy- Although the incidence of gastric cancer has been sub- tokines, which were implicated in many biological pro- stantially declining for several decades, it was still the cesses, such as migration of leukocytes, angiogenesis, fourth most common cancer and the second most fre- and tumor growth. The CCL chemokines represented quent cause of cancer death [1,2]. The high death rate the largest family of chemokines. They could attract was related to the difficulty of detecting gastric cancer at monocytes, macrophages, T cells, B cells, eosinophils, an early stage. Some serum tumor markers such as AFP, dendritic cells, mast cells and natural killer cells [3]. CEA, CA19-9, CA72-4, and CA50 were currently the CCL2 was a 76-amino acid protein that was originally puri- best clinical markers for gastric cancer. However, they fied and cloned from human gliomas and myelomonocytic were no good diagnostic tumor makers in early stage cells in 1989 [4]. CCL2 was the first chemokine discovered gastric cancer. Therefore, it was important to develop in the C-C subfamily of chemokines and was produced by new markers for detecting gastric cancer. a variety of cells. Some studies have implicated that CCL2 was an active participant in the tumor microenvironment [5,6]. CCL18 was a newly defined member of C-C sub- * Correspondence: [email protected] group of chemokines. It played an important role in in- †Equal contributors flammation and generation of the immune response. 1Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University However, the involvement of CCL18 in cancer was not Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, People’s Republic of China clear. 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China © 2013 Wu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Wu et al. BMC Clinical Pathology 2013, 13:15 Page 2 of 5 http://www.biomedcentral.com/1472-6890/13/15 Vascular endothelial growth factor (VEGF) was firstly groups were performed with Student’spairedt-test and isolated from the culture supernatant and the ascites of non-parametric Wilcoxon’s signed-rank test. Linear corre- rodent tumors a potent vascular permeability factor [7]. lations were assessed by calculating Pearson’scorrelation It was thought to be one of the most important factors coefficient or the non-parametric Spearman’s rho. The ac- promoting vascularization [8]. It played a role in both cepted level of significance was P <0.05. Statistical analyses physical and malignant conditions [9]. Previous studies and graphics were performed with the SPSS 13.0 statistical reported that serum VEGF level was high in several can- package (SPSS, Inc., Chicago, IL). cers, such as breast cancer and colon cancer [10,11]. The aim of this study was to investigate the relation- Results ship between the preoperative serum levels of CCL2, Clinicopathological characteristics CCL18, and VEGF, and the clinicopathological factors in There were 14 males and 6 females (2.33:1) with a mean patients with gastric cancer. age of 56 years in normal persons. There were 41 males and 19 females (2.16:1) with a mean age of 55 years. Methods There was 7 (11.7%) early gastric cancers and 53 (88.3%) Study population advanced gastric cancers. According to histological type, From July 2005 to December 2005, 60 patients who well-differentiated tumors were observed in 1 (1.7%) pa- underwent curative gastrectomy at department of Gas- tients, moderately-differentiated in 18 (30.0%) patients, tric Cancer and Soft Tissue Sarcoma in Shanghai Cancer and poorly-differentiated tumors in remaining 41 Hospital were included into this study. All patients were (68.3%) patients. Lymph node metastasis was observed confirmed as gastric cancer by preoperative biopsy. No pa- in 40 patients, the metastasis rate was 66.7%. The distri- tients received neoadjuvant treatment or preoperative bution of pathological stage was as follows: 11 (18.3%) blood transfusion. Additionally, 20 normal persons were patients belonged to stage I, 9 (15.1%) II, 23 (38.3%) III, designated as the control. Staging was performed according 17 (28.3%) IV. to the American Joint Committee on Cancer (AJCC) TNM Staging Classification for Carcinoma of the Stomach (6th edition, 2002). Data were retrieved from patients’ operative Serum CCL12, CCL18, and VEGF values and pathological reports. The written informed consent The serum values of CCL2, CCL18, and VEGF in normal had been obtained from all the patients, and this study was persons were 15.95 ± 1.15 (pg/ml), 42.46 ± 13.97 (pg/ml), approved by the Ethical Committee of Shanghai Cancer and 59.02 ± 6.28 (pg/ml), respectively. The serum values of Center of Fudan University. CCL2, CCL18, and VEGF in gastric cancers were 25.05 ± 1.22 (pg/ml), 115.94 ± 22.56 (pg/ml), and 132.92 ± 10.50 Blood samples (pg/ml), respectively. The levels were significantly higher in Blood samples were obtained by peripheral venous patients than that of control groups (Table 1). puncture on the day before operation. After clotting and within an hour of collection, the blood samples were Presence of malignancy centrifuged at 3000 g for 5 min and serum aliquots were Serum VEGF and CCL2 levels were significant inde- stored at -80°C until analysis. pendent predictors for the presence of gastric cancer. The optimal predictive model (χ2 =41.470, df =3, N =80, ELISA Negelkerke R2 =0.599, P <0.001) predicted presence of The measurement of CCL2, CCL18, and VEGF was performed using Quantikine human CCL2, CCL18, and Table 1 Comparisons of serum CCL2, CCL18, and VEGF VEGF sandwich enzyme-linked immunosorbent assay levels between gastric cancer patients and control (ELISA) kits (Genzyme Corporation, USA) according to groups the manufacturer’s instructions. All assays were duplicated. N Mean (pg/ml) Std. deviation P CCL2 < 0.001 Statistical analysis Patients 60 25.05 1.22 Continuous variables and categorical variables were Controls 20 15.95 1.15 expressed as mean ± 1 standard deviation and percentages, CCL18 < 0.001 respectively. The Kolmogorov-Smirnov test was used to Patients 60 115.94 22.56 assess whether the continuous variables conformed to a Controls 20 42.46 13.97 Gaussian pattern. Comparisons of continuous variables VEGF < 0.001 between independent groups were performed with Stu- Patients 60 132.92 10.50 dent’s unpaired t-test or Mann–Whitney non-parametric Controls 20 59.02 6.28 test. Comparisons of continuous variables between related Wu et al. BMC Clinical Pathology 2013, 13:15 Page 3 of 5 http://www.biomedcentral.com/1472-6890/13/15 malignancy with 93.3% sensitivity and 60.0% specificity. With a serum VEGF levels cut-off values ≥ 68.2 pg/ml, the sensitivity and specificity of VEGF to distinguish patients from controls were 83% and 60%, respect- ively. In contrast, with a serum CCL2 levels cut-off values ≥ 16.6 pg/ml, the sensitivity and specificity of CCL2 to distinguish patients from controls were 78% and 60%, respectively. With a cut-off value of ≥1272.8, the VEGF*CCL2 pre- dicted the presence of gastric cancer with 83% sensitivity and 80% specificity (Table 2). The concentrations prod- uct yielded the largest area under the ROC curve (0.895, P <0.001) (Figure 1). Correlation of preoperative serum markers and clinicopathological features Preoperative serum CCL2 was significantly correlated to age (r =0.433, P =0.001) and N stage (r = -0.266, P =0.040). Preoperative serum CCL18 was significantly P Figure 1 Combined ROC curve of serum CCL2 (area under the associated with histology type (r = -0.296, =0.022), N P P P curve 0.79, < 0.001), VEGF (area under the curve 0.83, <0.001) stage (r = -0.384, =0.002), and TNM stage (r = -0.386, and CCL2*VEGF cut-off values for the presence of gastric cancer.
Load more

Recommended publications
  • The Chemokine System in Innate Immunity
    Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The Chemokine System in Innate Immunity Caroline L. Sokol and Andrew D. Luster Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 Correspondence: [email protected] Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. Theyalso recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. hemokines are chemotactic cytokines that with emphasis placed on its role in the innate Ccontrol cell migration and cell positioning immune system. throughout development, homeostasis, and in- flammation. The immune system, which is de- pendent on the coordinated migration of cells, CHEMOKINES AND CHEMOKINE RECEPTORS is particularly dependent on chemokines for its function.
    [Show full text]
  • Rescuing Functional T Cells Induced by Growth Factor Deprivation, CCL2 Inhibits the Apoptosis Program
    CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells This information is current as Eva Diaz-Guerra, Rolando Vernal, M. Julieta del Prete, of September 24, 2021. Augusto Silva and Jose A. Garcia-Sanz J Immunol 2007; 179:7352-7357; ; doi: 10.4049/jimmunol.179.11.7352 http://www.jimmunol.org/content/179/11/7352 Downloaded from References This article cites 41 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/179/11/7352.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 September 24, 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 © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells1 Eva Diaz-Guerra,2 Rolando Vernal,2 M. Julieta del Prete,2 Augusto Silva, and Jose A. Garcia-Sanz3 The precise mechanisms involved in the switch between the clonal expansion and contraction phases of a CD8؉ T cell response remain to be fully elucidated.
    [Show full text]
  • Predictive Biomarkers for the Ranking of Pulmonary Toxicity of Nanomaterials
    nanomaterials Article Predictive Biomarkers for the Ranking of Pulmonary Toxicity of Nanomaterials Chinatsu Nishida 1, Hiroto Izumi 2, Taisuke Tomonaga 2 , Jun-ichi Takeshita 3 , Ke-Yong Wang 4, Kei Yamasaki 1, Kazuhiro Yatera 1 and Yasuo Morimoto 2,* 1 Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan; [email protected] (C.N.); [email protected] (K.Y.); [email protected] (K.Y.) 2 Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan; [email protected] (H.I.); [email protected] (T.T.) 3 Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan; [email protected] 4 Shared-Use Research Center, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-93-691-7136 Received: 3 September 2020; Accepted: 9 October 2020; Published: 15 October 2020 Abstract: We analyzed the mRNA expression of chemokines in rat lungs following intratracheal instillation of nanomaterials in order to find useful predictive markers of the pulmonary toxicity of nanomaterials. Nickel oxide (NiO) and cerium dioxide (CeO2) as nanomaterials with high pulmonary toxicity, and titanium dioxide (TiO2) and zinc oxide (ZnO) as nanomaterials with low pulmonary toxicity, were administered into rat lungs (0.8 or 4 mg/kg BW).
    [Show full text]
  • CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells1
    The Journal of Immunology CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells1 Eva Diaz-Guerra,2 Rolando Vernal,2 M. Julieta del Prete,2 Augusto Silva, and Jose A. Garcia-Sanz3 The precise mechanisms involved in the switch between the clonal expansion and contraction phases of a CD8؉ T cell response remain to be fully elucidated. One of the mechanisms implicated in the contraction phase is cytokine deprivation, which triggers apoptosis in these cells. CCR2 chemokine receptor is up-regulated following IL-2 deprivation, and its ligand CCL2 plays an essential role preventing apoptosis induced by IL-2 withdrawal not only in CTLL2 cells, but also in mouse Ag-activated primary CD8؉ T cells because it rescued functional CD8؉ T cells from deprivation induced apoptosis, promoting proliferation in response to subsequent addition of IL-2 or to secondary antigenic challenges. Thus, up-regulation of the CCR2 upon growth factor with- drawal together with the protective effects of CCL2, represent a double-edged survival strategy, protecting cells from apoptosis and enabling them to migrate toward sites where Ag and/or growth factors are available. The Journal of Immunology, 2007, 179: 7352–7357. espite the continuous generation of T lymphocytes in the is induced by TCR stimulation of naive T cells in the absence of body, their total number is tightly regulated, implying costimulatory signals. Such T cell death can be inhibited in vivo by D that T cells disappear at about the same rate as they are inflammation and in vitro by cytokines; bacterial products promote being produced.
    [Show full text]
  • CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction During Lung Metastasis Marko Roblek1, Darya Protsyuk1, Paul F
    Published OnlineFirst December 14, 2018; DOI: 10.1158/1541-7786.MCR-18-0530 Signal Transduction and Functional Imaging Molecular Cancer Research CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis Marko Roblek1, Darya Protsyuk1, Paul F. Becker2, Cristina Stefanescu1, Christian Gorzelanny3, Jesus F.Glaus Garzon1, Lucia Knopfova4,5, Mathias Heikenwalder2,6, Bruno Luckow7, Stefan W. Schneider3, and Lubor Borsig1 Abstract Increased levels of the chemokine CCL2 in cancer patients of vascular permeability induction was observed only in are associated with poor prognosis. Experimental evidence Ccr2ecKO mice. CCL2 stimulation of pulmonary endothe- suggests that CCL2 correlates with inflammatory monocyte lial cells resulted in increased phosphorylation of MLC2, recruitment and induction of vascular activation, but the endothelial cell retraction, and vascular leakiness that was functionality remains open. Here, we show that endothelial blocked by an addition of a CCR2 inhibitor. These data Ccr2 facilitates pulmonary metastasis using an endothelial- demonstrate that endothelial CCR2 expression is required specific Ccr2-deficient mouse model (Ccr2ecKO). Similar for tumor cell extravasation and pulmonary metastasis. levels of circulating monocytes and equal leukocyte recruit- fl/fl ment to metastatic lesions of Ccr2ecKO and Ccr2 litter- Implications: The findings provide mechanistic insight into mates were observed. The absence of endothelial Ccr2 how CCL2–CCR2 signaling in endothelial cells promotes their strongly reduced pulmonary metastasis, while the primary activation through myosin light chain phosphorylation, tumor growth was unaffected. Despite a comparable cyto- resulting in endothelial retraction and enhanced tumor cell fl/fl kine milieu in Ccr2ecKO and Ccr2 littermates the absence migration and metastasis. Introduction monocytic cells that contribute to formation of a metastatic niche (3–5).
    [Show full text]
  • Fbxw7 Increases CCL2/7 in CX3CR1 Macrophages to Promote Intestinal Inflammation
    Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation Jia He, … , Lihua Lai, Qingqing Wang J Clin Invest. 2019. https://doi.org/10.1172/JCI123374. Research In-Press Preview Immunology Inflammation Resident and inflammatory mononuclear phagocytes (MPh) with functional plasticity in the intestine are critically involved in the pathology of Inflammatory Bowel Diseases (IBD), in which the mechanism remains incompletely understood. In the present study, we found that increased expression of E3 ligase FBXW7 in the inflamed intestine was significantly correlated to IBD severity in both human diseases and mice model. Myeloid-Fbxw7 deficiency protected mice from dextran sodium sulfate (DSS) and 2,6,4-trinitrobenzene sulfonic acid (TNBS) induced colitis. Fbxw7 deficiency resulted in decreased production of chemokines CCL2 and CCL7 by colonic CX3CR1hi resident macrophages and reduced accumulation of CX3CR1int pro-inflammatory MPh in colitis colon tissue. Mice received AAV-shFbxw7 administration showed significantly improved survival rate and alleviated colitis. Mechanisms screening demonstrated that FBXW7 suppresses H3K27me3 modification and promotes Ccl2 and Ccl7 expression via degradation of histone-lysine N- methyltransferase EZH2 in macrophages. Taken together, our results indicate that FBXW7 degrades EZH2 and increases Ccl2/Ccl7 in CX3CR1hi macrophages, which promotes the recruiting CX3CR1int pro-inflammatory MPh into local colon tissues with colitis. Targeting FBXW7 might represent a potential therapeutic approach for intestine inflammation intervention. Find the latest version: https://jci.me/123374/pdf Fbxw7 increases CCL2/7 in CX3CR1hi macrophages to promote intestinal inflammation Jia He1,#, Yinjing Song1,#, Gaopeng Li1,#, Peng Xiao2, Yang Liu1, Yue Xue1, Qian Cao2, Xintao Tu1, Ting Pan1, Zhinong Jiang3, Xuetao Cao1,4, Lihua Lai1,*, and Qingqing Wang1,* Authors Affiliations 1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, P.
    [Show full text]
  • CCL2 and CXCL1 Trigger Calcitonin Gene-Related Peptide Release by Exciting Primary Nociceptive Neurons
    Journal of Neuroscience Research 82:51–62 (2005) CCL2 and CXCL1 Trigger Calcitonin Gene-Related Peptide Release by Exciting Primary Nociceptive Neurons Xiaomei Qin,1 You Wan,2 and Xian Wang1,3,4* 1Institute of Vascular Medicine, Peking University Third Hospital, Beijing, People’s Republic of China 2Neuroscience Research Institute, Basic Medical College, Peking University, Beijing, People’s Republic of China 3Department of Physiology, Basic Medical College, Peking University, Beijing, People’s Republic of China 4Key Laboratory of Molecular Cardiovascular Science of Education Ministry, Basic Medical College, Peking University, Beijing, People’s Republic of China Chemokines are important mediators in immune responses inflammation, whereas the release from terminals in the and inflammatory processes. Calcitonin gene-related pep- dorsal horn of the spinal cord modulates pain transmis- tide (CGRP) is produced in dorsal root ganglion (DRG) sion (Oku et al., 1987; Holzer, 1988). neurons. In this study, CGRP radioimmunoassay was used Chemokines are small, secreted proteins that stimu- to investigate whether the chemokines CCL2 and CXCL1 late the directional migration of leukocytes and mediate could trigger CGRP release from cultured DRG neurons of inflammation (Baggiolini et al., 1997). The chemokine neonatal rats and, if so, which cellular signaling pathway receptor family is the largest family of G-protein-coupled was involved. The results showed that CCL2 and CXCL1 receptors. Accordingly, the number of chemokines bind- (5–100 ng/ml) evoked CGRP release and intracellular ing these receptors is large, with >50 chemokine pepti- calcium elevation in a pertussis toxin (PTX)-sensitive man- des identified to date (Onuffer and Horuk, 2002). In ner.
    [Show full text]
  • COVID-19: Mechanisms of Vaccination and Immunity
    Review COVID-19: Mechanisms of Vaccination and Immunity Daniel E. Speiser 1,* and Martin F. Bachmann 2,3,4,* 1 Department of Oncology, University Hospital and University of Lausanne, 1066 Lausanne, Switzerland 2 International Immunology Centre, Anhui Agricultural University, Hefei 230036, China 3 Department of Rheumatology, Immunology and Allergology, Inselspital, University of Bern, 3010 Bern, Switzerland 4 Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland * Correspondence: [email protected] (D.E.S.); [email protected] (M.F.B.) Received: 2 July 2020; Accepted: 20 July 2020; Published: 22 July 2020 Abstract: Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy. Keywords: SARS-CoV-2; COVID-19; nucleic acid tests; serology; vaccination; immunity 1. Introduction The COVID-19 pandemic holds great challenges for which the world is only partially prepared [1]. SARS-CoV-2 combines serious pathogenicity with high infectivity. The latter is enhanced by the fact that asymptomatic and pre-symptomatic individuals can transmit the virus, in contrast to SARS-CoV-1 and MERS-CoV, which were transmitted by symptomatic patients and could be contained more efficiently [2,3].
    [Show full text]
  • GM-CSF Up-Regulates the Expression of CCL2 by T Lymphocytes in Mammary Tumor-Bearing Mice
    129-136 2/6/07 11:42 Page 129 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 20: 129-136, 2007 129 GM-CSF up-regulates the expression of CCL2 by T lymphocytes in mammary tumor-bearing mice JENNIFER L. OWEN1, MARTA TORROELLA-KOURI 2, MARY E. HANDEL-FERNANDEZ2 and VIJAYA IRAGAVARAPU-CHARYULU1 1Department of Basic Biomedical Sciences, Florida Atlantic University, Boca Raton, FL 33431; 2Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA Received January 16, 2007; Accepted February 23, 2007 Abstract. MCP-1/CCL2 (monocyte chemoattractant protein- the appropriate activation of these cells. Chemokines are a 1/CC chemokine ligand 2) is a ß or CC chemokine that is group of inducible, proinflammatory cytokines that interact expressed by a variety of cell types, including fibroblasts, with leukocytes and recruit them into the tumor. Clinically, endothelial, smooth muscle, and glial cells. In addition, cells elevated levels of chemokines have been found in a variety involved in immunity, such as monocytes/macrophages, of inflammatory diseases including cancer (1). The prototype neutrophils, and eosinophils have also been shown to express CC chemokine is a monocyte chemoattractant protein-1 this chemoattractant. Using a murine model of the D1- (MCP-1/CCL2) that was first identified as a potent chemo- DMBA-3 mammary adenocarcinoma, we demonstrated the taxin for monocytes (2) and is also a chemotactic for activated unique production of CCL2 by splenic T lymphocytes from T lymphocytes, natural killer cells, and basophils (3-5). This tumor-bearing animals. Because this tumor produces chemokine is synthesized by a variety of cell types in response GM-CSF, and this factor is also up-regulated in the B to various stimuli including cytokines.
    [Show full text]
  • Regulation of Adipose Tissue Inflammation by Interleukin 6
    Regulation of adipose tissue inflammation by INAUGURAL ARTICLE interleukin 6 Myoung Sook Hana, Alexis Whitea, Rachel J. Perryb,c, Joao-Paulo Camporezb,c, Juan Hidalgod, Gerald I. Shulmanb,c, and Roger J. Davisa,1 aProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605; bDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520; cDepartment of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06520; and dDepartment of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autonoma de Barcelona, Bellaterra, 08193 Barcelona, Spain This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2018. Contributed by Roger J. Davis, December 19, 2019 (sent for review November 15, 2019; reviewed by Robert E. Lewis and Evan D. Rosen) Obesity is associated with a chronic state of low-grade inflammation Indeed, tissue-specific knockout mice confirm that IL6 plays an and progressive tissue infiltration by immune cells and increased important role in the obesity response (15–23). expression of inflammatory cytokines. It is established that inter- While insight concerning the complex actions of IL6 on me- leukin 6 (IL6) regulates multiple aspects of metabolism, including tabolism has been obtained, the consequences of IL6 production glucose disposal, lipolysis, oxidative metabolism, and energy expen- by specific tissues is poorly understood because the source of IL6 diture. IL6 is secreted by many tissues, but the role of individual cell under many physiological conditions has not been established. It types is unclear. We tested the role of specific cells using a mouse is known that adipose tissue represents a major source of increased model with conditional expression of the Il6 gene.
    [Show full text]
  • CXCL4/Platelet Factor 4 Is an Agonist of CCR1 and Drives Human Monocyte Migration
    This is a repository copy of CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/132464/ Version: Published Version Article: Fox, James Martin orcid.org/0000-0002-2473-7029, Kausar, Fahima, Day, Amy et al. (7 more authors) (2018) CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific Reports. 9466. ISSN 2045-2322 Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ www.nature.com/scientificreports OPEN CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration Received: 10 March 2016 James M. Fox 1,3, Fahima Kausar1, Amy Day1, Michael Osborne1, Khansa Hussain1, Accepted: 5 June 2018 Anja Mueller1,4, Jessica Lin1, Tomoko Tsuchiya 2, Shiro Kanegasaki2 & James E. Pease1 Published: xx xx xxxx Activated platelets release micromolar concentrations of the chemokine CXCL4/Platelet Factor-4. Deposition of CXCL4 onto the vascular endothelium is involved in atherosclerosis, facilitating monocyte arrest and recruitment by an as yet, unidentified receptor.
    [Show full text]
  • The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity Wendy A
    The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity Wendy A. Szymczak and George S. Deepe, Jr This information is current as J Immunol 2009; 183:1964-1974; Prepublished online 8 July of September 29, 2021. 2009; doi: 10.4049/jimmunol.0901316 http://www.jimmunol.org/content/183/3/1964 Downloaded from References This article cites 57 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/183/3/1964.full#ref-list-1 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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity1 Wendy A. Szymczak*† and George S. Deepe, Jr.2*‡ Expression of the chemokine receptor CCR2 can be detrimental or beneficial for infection resolution.
    [Show full text]