			Home About us Contact

Inflammatory Chemokines (inflammatory + chemokine)

Distribution by Scientific Domains

Medical Sciences	87%

Selected Abstracts

CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune system

INFLAMMATORY BOWEL DISEASES, Issue 4 2010
Iris Dotan MD
Abstract Background: Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Methods: Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. Results: IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. Conclusions: CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;) [source]

Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis

EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009
J. Kuhle
Background and purpose:, Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. Methods:, We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1, (MIP-1,), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. Results:, MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = ,0.407; P = 0.075). Conclusions:, We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease. [source]

Analysis of differential immune responses induced by innate and adaptive immunity following transplantation

IMMUNOLOGY, Issue 2 2003
Hongzhen He
Summary The roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up-regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up-regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation. [source]

CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune system

Statins and progressive renal disease

MEDICINAL RESEARCH REVIEWS, Issue 1 2002
Michele Buemi
Abstract Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans. © 2001 John Wiley & Sons, Inc. Med Res Rev, 22, No. 1, 76,84, 2002 [source]

Chemokine Signaling to Lymphocyte Integrins Under Shear Flow

MICROCIRCULATION, Issue 1 2009
RONEN ALON
ABSTRACT The arrest of lymphocytes at target vascular sites depends on the rapid activation of their integrins by specialized endothelial chemokines. For over a decade, the mechanisms by which these chemokines trigger initial integrin-mediated adhesiveness and subsequent adhesion strengthening and crawling over endothelial surfaces have been dissected in vitro using flow chamber setups. These studies revealed that lymph node chemokines and subsets of inflammatory chemokines, collectively termed "arrest chemokines," can trigger the fastest measurable inside-out integrin activation events. Recent studies indicate that shear forces applied on lymphocytes are instrumental in these rapid activation processes. Different GTPases have been implicated in these activation processes. As these enzymes contribute to successive integrin activation and redistribution processes in both early and prolonged contacts there is a growing need to dissect in vitro and validate in vivo specific signaling routes involved in early and late integrin activation events controlling lymphocyte arrest and their subsequent crawling to sites of diapedesis. In this article, we present an overview of both early and recent shear-flow studies of integrin activation in lymphocytes and discuss future perspectives of integrin activation research in vitro and in vivo. [source]

Expression of CCL5 (RANTES) and CCR5 in prostate cancer,

THE PROSTATE, Issue 2 2006
Gayle G. Vaday
Abstract Background Expression of the inflammatory chemokine CCL5 (RANTES) by tumor cells is thought to correlate with the progression of several cancers. CCL5 was shown to induce breast cancer cell migration, mediated by the receptor CCR5. A CCR5 antagonist was demonstrated to inhibit experimental breast tumor growth. Recently, CCL5 and CCR5 mRNA expression was reported in prostate cancer (PCa) tissues. Herein, we characterized CCL5 and CCR5 expression in cultures of PCa cells and explored possible functions of CCL5 in PCa progression. Methods Quantitative RT-PCR, ELISA, and immunohistochemical staining were performed to examine CCL5 expression in prostate cell lines. CCR5 expression was measured by flow cytometry. Proliferation and invasion assays were performed to determine potential functions of CCL5 and CCR5 in PCa. Results Expression of CCL5 mRNA and protein was found in human PCa cell lines (PC-3; DU-145; LNCaP) and primary prostate adenocarcinoma cells. CCL5 and CCR5 were also detected in human PCa tissues. CCR5 expression was demonstrated on the cell surface of PCa cells, as well as in intracellular pools. Incubation with CCL5 (10,100 ng/ml) induced PCa cell proliferation, and the CCR5 antagonist TAK-779 inhibited CCL5-induced proliferation. CCL5 was found to stimulate PCa cell invasion, and TAK-779 blocked the effects of CCL5. Conclusions In light of evidence that inflammation influences the pathogenesis of PCa, these results suggest that inflammatory chemokines, such as CCL5, expressed by prostate cells may act directly on the growth and survival of PCa cells. Chemokine receptor antagonists may thus block autocrine mechanisms of PCa progression. Published 2005 Wiley-Liss, Inc. [source]

Specific central nervous system recruitment of HLA-G+ regulatory T cells in multiple sclerosis,

ANNALS OF NEUROLOGY, Issue 2 2009
Yu-Hwa Huang MSci
Objective We have recently described a novel population of natural regulatory T cells (Treg) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-Gpos Treg). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). Methods Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-Gpos Treg were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB). Results HLA-Gpos Treg were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-Gpos Treg showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-Gpos Treg of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing Treg, HLA-Gpos Treg derived from peripheral blood were functionally unimpaired in MS. Interpretation In MS, HLA-Gpos Treg may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS. Ann Neurol 2009 [source]