Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cloned human CD4+ T cell lines specific for the house dust mite Dermatophagoides pteronyssinus were used to map minimal T cell activation-inducing epitopes on the Group I allergen in D. pteronyssinus extracts (Der p I) molecule. Most of these Der p I-specific T cell clones expressed different TCR V alpha and V beta gene products. Using recombinant deletion proteins, three T cell epitopes were identified on the Der p I molecule; p45-67 and p117-143 were recognized by HLA-DR7-restricted T cells, whereas p94-104 was recognized in the context of HLA-DR2, DRw11 (DR5), and -DR8 molecules. This degenerate class II MHC restriction appears to be due to shared Phe and Asp residues at positions 67 and 70, respectively, in the third variable domain of the HLA-DR beta chain. All three T cell epitopes induced Th2-like cytokine production profiles by the Der p I-specific T cell clones, which were characterized by the production of very high levels of IL-4 and IL-5, as compared with those secreted by tetanus toxin-specific T cell clones derived from the same patients, but no or low amounts of IL-2 and IFN-gamma. This Th2-like production profile was, however, not an intrinsic property of the Der p I-specific T cells, but was dependent upon their mode of activation. Stimulation with Con A also induced very low or no measurable levels of IL-2 and IFN-gamma, whereas activation with TPA and the calcium ionophore A23187 resulted in the production of high levels of IL-4, IL-5, IL-2, and IFN-gamma. These results indicate that Der p I-specific T cell clones are not defective in their capacity to produce high levels of Th1 cytokines.
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PMID:T cell activation-inducing epitopes of the house dust mite allergen Der p I. Proliferation and lymphokine production patterns by Der p I-specific CD4+ T cell clones. 137 May 14

Human dermal microvascular endothelial cells (HDMEC) play a central role in many aspects of the inflammatory and immune reactions in skin. HDMEC display a phenotypic diversity ranging from cells with an epithelioid morphology to those that show both morphologic and biochemical characteristics of macrophages. Here it is shown that HDMEC possess the capability to both process and present Ags. T lymphocyte clones specific for peptide p94-104, which are derived from the protein of group I allergen of Dermatophagoides pteronyssinus, a major house dust mite allergen, and restricted by HLADR11, proliferated specifically to stimulation with the group I allergen of D. pteronyssinus and with peptide p94-104 presented by HDMEC. Preincubation for 48 h with IFN-gamma enhanced the expression of class II MHC Ags on HDMEC, which in turn increased the capacity of HDMEC to present Ag. When HDMEC were primed with Ag in the presence of IL-10, a 75% inhibition of Ag-specific T cell proliferation was observed. IL-10 also inhibited T cell proliferation induced by IFN-gamma-stimulated HDMEC. These findings demonstrate that HDMEC possess the ability to process and present Ag to CD4+ T cells and that these reactions are stimulated by IFN-gamma and inhibited by IL-10. The reduced Ag-presenting capacity of HDMEC mediated by IL-10 is not associated with a down-regulation of class II MHC expression. No significant reduction of HLA-DR expression was detected either at the protein or gene level when HDMEC were incubated with IFN-gamma and IL-10 as compared with incubation with IFN-gamma alone. The profound down-regulatory effect of IL-10 on Ag presentation may provide a new pharmacologic approach to control inflammatory responses in skin.
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PMID:Antigen presentation by human dermal microvascular endothelial cells. Immunoregulatory effect of IFN-gamma and IL-10. 820 3

IFN-gamma plays a role in the response to melanoma indirectly through its effect on the immune system and directly through its antiproliferative and proapoptotic effects on melanoma cells. To understand the molecular basis for the direct antimelanoma effect of IFN-gamma, we studied IFN-induced changes in gene expression and signaling among three human melanoma cell lines (DM6, DM93, and 501mel). These were resistant to the antimelanoma effect of IFN-alpha, and only DM6 cells exhibited growth inhibition and apoptosis with IFN-gamma. Through DNA microarray analysis, we found that the antimelanoma effect of IFN-gamma in DM6 was associated with the down-regulation of multiple genes involved in G-protein signaling and phospholipase C activation (including Rap2B and calpain 3) as well as the down-regulation of genes involved in melanocyte/melanoma survival (MITF and SLUG), apoptosis inhibition (Bcl2A1 and galectin-3), and cell cycling (CDK2). The antimelanoma effect of IFN-gamma was also associated with the up-regulation of the proapoptotic dependence receptor UNC5H2 and the Wnt inhibitor Dkk-1. Whereas both IFNs were able to activate Stat1 in all cell lines, the delayed activation of the extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases occurred only in DM6 with IFN-gamma, and the effect of IFN-gamma on cell growth and survival as well as gene expression in DM6 was dependent on the coordinate activation of MEK1 and p38. These findings provide new insights into the signaling events and gene expression changes associated with growth inhibition and apoptosis in melanoma and may thereby assist in identifying new targets for the treatment of melanoma.
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PMID:Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. 1620 58