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)

Nurse-like stromal cell lines from the synovial tissue of patients with rheumatoid arthritis (RA-SNC) produce, on coculture with lymphocytes, large amounts of proinflammatory cytokines. In the present paper, we analyze the molecular events necessary for the induction of cytokine release from RA-SNC cells, and particularly the roles played by cell adhesion and the transmigration (also known as pseudoemperipolesis) of lymphocytes. For this purpose, the effects of various mAbs on the binding and transmigration of a human B-cell line, MC/car, were examined using a cloned RA-SNC line, RA-SNC77. To analyze the role of lymphocyte binding and transmigration on upregulated cytokine production by the RA-SNC77 cells, we used C3 exoenzyme-treated MC/car cells, which could bind to RA-SNC77 cells but could not transmigrate. Treatment with anti-CD29 or anti-CD49d mAb significantly reduced binding and transmigration of the MC/car cells. In contrast, the neutralizing anti-CD106/vascular cell adhesion molecule 1 mAb did not show any inhibitory effect. Likewise, none of the neutralizing mAbs against CD11a, CD18, CD44, CD49e, or CD54 showed significant effects. Binding of C3-treated or untreated MC/car cells to RA-SNC77 cells induced comparable levels of IL-6 and IL-8 production. In addition, the enhanced cytokine production by RA-SNC77 cells required direct lymphocyte contact via a very late antigen-4 (VLA-4)-independent adhesion pathway. These results indicate that, although both the VLA-4-dependent/vascular cell adhesion molecule 1-independent and the VLA4-independent adhesion pathways are involved in MC/car binding and subsequent transmigration, only the VLA4-independent adhesion pathway is necessary and sufficient for the enhanced proinflammatory cytokine production by RA-SNC77 cells. The transmigration process, which is dependent on Rho-GTPase, is not a prerequisite for this phenomenon.
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PMID:VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients. 1245 13

RUNX proteins are heterodimeric factors that play crucial roles during development and differentiation of cells of the immune system. The RUNX3 transcription factor controls lineage decisions during thymopoiesis and T-cell differentiation, and modulates myeloid cell effector functions. We now report the characterization of the human RUNX3/p33 isoform, generated by splicing out a Runt DNA-binding domain-encoding exon, and whose transcriptional activities differ from those of the prototypic RUNX3/p44 molecule. Unlike RUNX3/p44, RUNX3/p33 is induced upon maturation of monocyte-derived dendritic cells (MDDC), and is unable to transactivate the regulatory regions of the CD11a, CD11c and CD49e integrin genes. Overexpression of RUNX3/p33 in myeloid cell lines led to diminished expression of genes involved in inflammatory responses. Moreover, overexpression of RUNX3/p33 down-modulated the basal level of IL-8 production from immature monocyte-derived dendritic cells (MDDC). Besides, siRNA-mediated knock-down of RUNX3 led to diminished levels of IL-8 RNA in immature MDDC, and modulated the neutrophil-recruiting capacity of myeloid cell line supernatants. Since IL-8 promotes neutrophil chemotaxis and degranulation during inflammatory responses, and exerts mitogenic and angiogenic actions within tumor microenvironment, our results imply that myeloid RUNX3 expression regulates the recruitment of leukocytes towards inflammatory foci and might also contribute to human cancer progression.
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PMID:The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression. 2061 77


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