Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts can acquire an immunoregulatory phenotype and they play an important role in triggering and upholding inflammation. Yet, the mechanism of this immunoactivation remains unknown. Previously we showed that spheroid formation by human fibroblasts leads to nemosis: activation through upregulation of cyclooxygenase-2, production of growth factors, and proteolysis. We now show that clustering of fibroblasts to spheroids leads to a significant induction of chemotactic cytokines able to attract various leukocyte subtypes. The mRNA contents of several chemokines (CCL2-5, CXCL1-3, and CXCL8) were 6-169-fold higher in fibroblast spheroids than in monolayer controls 36 h after spheroid formation. Similarly, CCL3, CCL5 and CXCL8 levels in spheroid medium were significantly higher than in monolayer medium. Conditioned fibroblast spheroid medium induced chemotaxis of primary human neutrophils and monocyte-like THP-1 cells, and the effects were significantly inhibited by antibodies against CXCL8 and the chemokine receptor CCR1, respectively. The decreased levels of IkappaB alpha and presence of DNA-binding nuclear factor-kappaB (NF-kappaB) after spheroid formation indicate NF-kappaB activity. In conclusion, clustering of fibroblasts provides an experimental model to study their activation and is sufficient to induce substantial proinflammatory chemokine secretion functionally promoting leukocyte migration, and the mechanism seems to involve the NF-kappaB signalling pathway.
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PMID:Clustering of fibroblasts induces proinflammatory chemokine secretion promoting leukocyte migration. 1924 98

The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.
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PMID:Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses. 2352 47

LIGHT is known to act as a novel mediator for atherogenesis. Furthermore, it has been reported that emodin, an active component extracted from rhubarb, can stop the growth of cancer cells. However, it is not known if emodin exerts anti-atherogenic effects in the human monocyte, THP-1, following treatment with LIGHT. In this study, we evaluated the inhibitory effect of emodin and rhein on LIGHT-induced migration in THP-1. Emodin and rhein decreased the level of LIGHT-induced generation of ROS, as well as the expression of CCR1, CCR2 and ICAM-1 and the production of IL-8, MCP-1, TNF-alpha, and IL-6. Emodin and rhein also decreased the phosphorylation of the p38 MAPK and IkB-alpha. Furthermore, the NADPH oxidase assembly inhibitor, AEBSF, and the blocker of NADPH oxidase, p47(phox) small interference RNA (siRNA), also efficiently blocked LIGHT-induced migration, CCR1, CCR2, ICAM-1, and HVEM expression, and p38 MAPK and NF-kB activation. These findings indicate that the inhibitory effects of emodin and rhein on LIGHT-induced migration occur via decreasing ROS production and NADPH oxidase p47(phox) activation. Taken together, these results indicate that emodin and rhein have the potential for use as an anti-atherosclerosis agent.
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PMID:Emodin and rhein inhibit LIGHT-induced monocytes migration by blocking of ROS production. 2029 10


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