Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chemokine, monocyte chemoattractant protein 1 (MCP-1), attracts macrophages. The production of MCP-1 is enhanced in keratinocytes of psoriatic lesions, which may contribute to macrophage infiltration into the lesions. It is known that estrogen regulates the course of psoriasis. We examined in vitro effects of 17beta-estradiol (E2) on MCP-1 production by human keratinocytes. E2 inhibited constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced MCP-1 secretion, mRNA expression, and promoter activity in keratinocytes, and these effects of E2 were counteracted by estrogen receptor antagonist ICI 182 780. GC-rich Sp1 element and activator protein 1 (AP-1) element on MCP-1 promoter were required for constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced transcription, respectively, and involved in transrepression by E2. E2 inhibited constitutive Sp1 and 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 transcriptional activities whereas it did not inhibit DNA binding of Sp1 or AP-1 c-Fos/c-Jun. E2 inhibited Sp1 and AP-1 transcriptional activities and MCP-1 promoter activity in estrogen receptor beta (ERbeta) transfected SKBR3 cells. Deletion of the A/B region or mutation of activation function 2 in ERbeta abrogated E2-dependent transcriptional inhibition by ERbeta whereas mutation of DNA-binding domain retained the inhibitory effects. Transfection of ERbeta enhanced the inhibitory effects of E2 on Sp1 and AP-1 transcriptional activities and MCP-1 promoter activities in nontransfected keratinocytes. Coimmunoprecipitation studies showed an E2-dependent association of ERbeta with Sp1 or AP-1 in ERbeta-transfected keratinocytes. These results suggest that E2-bound ERbeta may inhibit MCP-1 gene expression by inhibiting Sp1 and AP-1 transcriptional activities in keratinocytes. A/B region and intact activation function 2 of ERbeta may be responsible for the effects of E2.
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PMID:17Beta-estradiol inhibits MCP-1 production in human keratinocytes. 1278 35

We have previously shown that 17beta-estradiol (E2) attenuates responses to endoluminal injury of the rat carotid artery, at least in part, by decreasing inflammatory mediator expression and neutrophil infiltration into the injured vessel, with a major effect on the neutrophil-specific chemokine cytokine-induced neutrophil chemoattractant (CINC)-2 beta. Current studies tested the hypothesis that activated rat aortic smooth muscle cells (RASMCs) express these same inflammatory mediators and induce neutrophil migration in vitro and that E2 inhibits these processes by an estrogen receptor (ER)-dependent mechanism. Quiescent RASMCs treated with E2, the ER alpha-selective agonist propyl pyrazole triol (PPT), the ER beta-selective agonist diarylpropiolnitrile (DPN), or vehicle for 24 h were stimulated with tumor necrosis factor (TNF)-alpha and processed for real-time RT-PCR, ELISA, or chemotaxis assays 6 h later. TNF-alpha stimulated and E2 attenuated mRNA expression of inflammatory mediators, including P-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, monocyte chemoattractant protein (MCP)-1, and CINC-2 beta. DPN dose dependently attenuated TNF-alpha-induced mRNA expression of CINC-2 beta, whereas PPT had no effect. The anti-inflammatory effects of DPN and E2 were blocked by the nonselective ER-inhibitor ICI-182,780. ELISA confirmed the TNF-alpha-induced increase and E2-induced inhibition of CINC-2 beta protein secretion. TNF-alpha treatment of RASMCs produced a twofold increase in neutrophil chemotactic activity of conditioned media; E2 and DPN treatment markedly inhibited this effect. E2 inhibits activated RASMC proinflammatory mediator expression and neutrophil chemotactic activity through an ER beta-dependent mechanism.
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PMID:Estrogen modulates TNF-alpha-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-beta activation. 1735 Oct 72

Because studies have shown that 17beta-estradiol (E2) produces anti-inflammatory effects after various adverse circulatory conditions, we examined whether administration of E2 before spinal cord injury (SCI) has any salutary effects in reducing SCI. Spinal cord injury was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of E2, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) expression of iNOS, nitrotyrosine, and COX-2; (4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining and Bax and Bcl-2 expression); and (5) tissue TNF-alpha, IL-6, IL-1beta, and monocyte chemoattractant protein 1 levels. In another set of experiments, the pretreatment or posttreatment with E2 significantly ameliorates the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of E2 were mediated via the estrogen receptors, we investigated the effect of an estrogen receptor antagonist, ICI 182,780, on the protective effects of E2. ICI 182,780 (500 microg/kg, s.c., 1 h before treatment with E2) significantly antagonized the effect of the E2 and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of E2 before SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.
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PMID:Effect of 17beta-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. 1770 35