scholarly journals Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1–dependent leukocyte recruitment in vivo

2008 ◽  
Vol 205 (8) ◽  
pp. 1739-1746 ◽  
Author(s):  
Daxin Chen ◽  
Adam Carpenter ◽  
Joel Abrahams ◽  
Rachel C. Chambers ◽  
Robert I. Lechler ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Mouse Heart ◽  
Protease Activated Receptors ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cell Recruitment ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Protease Activated Receptor 1

Thrombin, acting through a family of protease-activated receptors (PARs), is known to amplify inflammatory responses, but the in vivo importance of PARs in inflammation is not fully appreciated. In a mouse heart-to-rat transplant model, where it is possible to distinguish graft (mouse) from systemic (rat) chemokines, we show that donor PAR-1 is required to generate the local monocyte chemoattractant protein (MCP)-1 needed to recruit rat natural killer cells and macrophages into the hearts. We have confirmed the importance of this mechanism in a second model of thioglycollate-induced peritonitis and also show that PAR-1 is important for the production of MCP-3 and MCP-5. Despite the presence of multiple other mediators capable of stimulating chemokine production in these models, these data provide the first evidence that thrombin and PAR activation are required in vivo to initiate inflammatory cell recruitment.

scholarly journals Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog by injection of human RANTES but not human monocyte chemoattractant protein 1, human macrophage inflammatory protein 1 alpha, or human interleukin 8.

1993 ◽  
Vol 178 (6) ◽  
pp. 1913-1921 ◽  
Author(s):  
R Meurer ◽  
G Van Riper ◽  
W Feeney ◽  
P Cunningham ◽  
D Hora ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Interleukin 8 ◽  
Human Macrophage ◽  
Binding Studies ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Equilibrium binding studies on canine mononuclear and granulocytic cells allow the identification of a single high affinity receptor for the human C-C chemokine RANTES (dissociation constant, 14 +/- 8 pM), that, in contrast to the human RANTES receptor, has no affinity for human macrophage inflammatory protein 1 alpha (hMIP-1 alpha). A single intradermal injection of hRANTES in dog resulted in eosinophil- and macrophage-rich inflammatory sites within 4 h. Cell infiltration peaked at 16-24 h after hRANTES injection. There was histological evidence of intravascular activation of eosinophils at 4 h, although eosinophils in the vasculature and interstitium contained apparently intact granules. Monocytes were the predominant cells adherent to venular endothelium at 16-24 h. Human MIP-1 alpha elicited no response in canine dermis, whereas monocyte chemoattractant protein 1 caused mild perivascular cuffing with monocytes. In contrast, human interleukin 8 induced a neutrophilic dermal infiltrate that was maximal by 4 h after challenge. This provides the first direct evidence in vivo that RANTES has significant proinflammatory activity and, in addition, could be a mediator in atopic pathologies characterized by eosinophilic and monocytic inflammatory responses.

Cyclopentenone Prostaglandins Inhibit Cytokine-Induced NF-κB Activation and Chemokine Production by Human Mesangial Cells

2001 ◽  
Vol 12 (8) ◽  
pp. 1659-1667
Author(s):  
BRAD H. ROVIN ◽  
LING LU ◽  
ANNA COSIO
Keyword(s):  
Inflammatory Response ◽  
Mesangial Cells ◽  
Gene Activation ◽  
Chemokine Production ◽  
Human Mesangial Cells ◽  
Renal Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Cyclopentenone Prostaglandins

Abstract. In the kidney an uncontrolled inflammatory response to an acute insult may lead to chronic inflammation, permanent tissue damage, and progressive renal insufficiency. Resolution of acute inflammation likely is dependent on endogenous regulatory mechanisms activated in parallel with mediators of renal inflammation. These mechanisms are postulated to attenuate the renal expression of proinflammatory cytokines, including the chemokines responsible for recruiting leukocytes to the kidney, thus facilitating the transition from inflammation to healing. To understand the regulation of the inflammatory response within the kidney, the effects of anti-inflammatory J series cyclopentenone prostaglandins on chemokine production by human mesangial cells were examined. Treatment of mesangial cells with prostaglandin J2and 15-deoxy-Δ12,14-prostaglandin J2blocked interleukin-1β—induced monocyte chemoattractant protein-1 mRNA expression and protein production. This correlated with failure of the transcription factor nuclear factor-κB (NF-κB) to translocate to the nucleus and bind to its recognition motif, a step required for cytokine-induced monocyte chemoattractant protein-1 gene activation. NF-κB failed to translocate because the cyclopentenone prostaglandins attenuated degradation of the NF-κB inhibitor IκB-α. These data suggest that certain prostaglandins can limit the extent of renal chemokine expression and thus may have an important role in resolving renal inflammation.

Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1)in vivo andin vitro

1994 ◽  
Vol 58 (2) ◽  
pp. 240-247 ◽  
Author(s):  
Isabelle Desbaillets ◽  
Mitsuhiro Tada ◽  
Nicolas De Tribolet ◽  
Annie-Claire Diserens ◽  
Marie-France Hamou ◽  
...  
Keyword(s):  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Human Astrocytomas

Angiotensin II induces monocyte chemoattractant protein-1 expression via a nuclear factor-κB-dependent pathway in rat preadipocytes

2006 ◽  
Vol 291 (4) ◽  
pp. E771-E778 ◽  
Author(s):  
Kyoichiro Tsuchiya ◽  
Takanobu Yoshimoto ◽  
Yuki Hirono ◽  
Toru Tateno ◽  
Toru Sugiyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Luciferase Assay ◽  
Ang Ii ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Dependent Pathway

Both monocyte chemoattractant protein-1 (MCP-1), a member of chemokine family, and angiotensinogen, a precursor of angiotensin (ANG) II, are produced by adipose tissue and increased in obese state. MCP-1 has been shown to decrease insulin-stimulated glucose uptake and several adipogenic genes expression in adipocytes in vitro, suggesting its pathophysiological significance in obesity. However, the pathophysiological interaction between MCP-1 and ANG II in adipose tissue remains unknown. The present study was undertaken to investigate the potential mechanisms by which ANG II affects MCP-1 gene expression in rat primary cultured preadipocytes and adipose tissue in vivo. ANG II significantly increased steady-state MCP-1 mRNA levels in a time- and dose-dependent manner. The ANG II-induced MCP-1 mRNA and protein expression was completely abolished by ANG II type 1 (AT1)-receptor antagonist (valsartan). An antioxidant/NF-κB inhibitor (pyrrolidine dithiocarbamate) and an inhibitor of 1κB-α phosphorylation (Bay 11-7085) also blocked ANG II-induced MCP-1 mRNA expression. ANG II induced translocation of NF-κB p65 subunit from cytoplasm to nucleus by immunocytochemical study. Luciferase assay using reporter constructs containing MCP-1 promoter region revealed that two NF-κB binding sites in its enhancer region were essential for the ANG II-induced promoter activities. Furthermore, basal mRNA and protein of MCP-1 during preadipocyte differentiation were significantly greater in preadipocytes than in differentiated adipocytes, whose effect was more pronounced in the presence of ANG II. Exogenous administration of ANG II to rats led to increased MCP-1 expression in epididymal, subcutaneous, and mesenteric adipose tissue. In conclusion, our present study demonstrates that ANG II increases MCP-1 gene expression via ANG II type 1 receptor-mediated and NF-κB-dependent pathway in rat preadipocytes as well as adipose MCP-1 expression in vivo. Thus the augmented MCP-1 expression by ANG II in preadipocytes may provide a new link between obesity and cardiovascular disease.

scholarly journals Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 1053-1059 ◽  
Author(s):  
Frank M. Szaba ◽  
Stephen T. Smiley
Keyword(s):  
Inflammatory Responses ◽  
Direct Injection ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Macrophage Adhesion ◽  
Pleiotropic Functions ◽  
Deficient Mice

Abstract Extravascular coagulation leading to fibrin deposition accompanies many immune and inflammatory responses. Although recognized by pathologists for decades, and probably pathologic under certain conditions, the physiologic functions of extravascular coagulation remain to be fully defined. This study demonstrates that thrombin can activate macrophage adhesion and prompt interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production in vivo. Peritoneal macrophages were elicited with thioglycollate (TG) and then activated in situ, either by intraperitoneal injection of lipopolysaccharide (LPS) or by injection of antigen into mice bearing antigen-primed T cells. Others previously established that such treatments stimulate macrophage adhesion to the mesothelial lining of the peritoneal cavity. The present study demonstrates that thrombin functions in this process, as macrophage adhesion was suppressed by Refludan, a highly specific thrombin antagonist, and induced by direct peritoneal administration of purified thrombin. Although recent studies established that protease activated receptor 1 (PAR-1) mediates some of thrombin's proinflammatory activities macrophage adhesion occurred normally in PAR-1–deficient mice. However, adhesion was suppressed in fibrin(ogen)-deficient mice, suggesting that fibrin formation stimulates macrophage adhesion in vivo. This study also suggests that fibrin regulates chemokine/cytokine production in vivo, as direct injection of thrombin stimulated peritoneal accumulation of IL-6 and MCP-1 in a fibrin(ogen)-dependent manner. Given that prior studies have clearly established inflammatory roles for PAR-1, thrombin probably has pleiotropic functions during inflammation, stimulating vasodilation and mast cell degranulation via PAR-1, and activating cytokine/chemokine production and macrophage adhesion via fibrin(ogen).

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