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Decreased NF (decreased + nf)
Selected AbstractsEffect of heme oxygenase-1 induction by octreotide on TNBS-induced colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2007im Erbil Abstract Background and Aim:, Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Although the precise etiology of ulcerative colitis remains unknown, it is believed to involve an abnormal host response to endogenous or environmental antigens, genetic factors, and oxidative damage. The aim of the present study was to investigate whether heme oxygenase-1 (HO-1) induction by octreotide could protect against oxidative and inflammatory damage from induced colitis. Methods:, Rats received octreotide 50 µg/kg per day intraperitoneally for 5 days before 2,4,6 trinitrobenzene sulfonic acid (TNBS) solution administration and for 15 days following TNBS solution administration. Rats were killed on day 21, and colonic malondialdehyde (MDA) levels, glutathione (GSH) levels and HO-1 expression were measured. Nuclear factor (NF)-,B and HO-1 expression was evaluated by immunohistochemical examination of the colonic tissue. Results:, Rats with TNBS-induced colitis had significantly increased colonic MDA levels and HO-1 expression in comparison to the control group. Octreotide treatment was associated with increased HO-1 expression and GSH levels, but decreased MDA levels. Histopathological examination revealed that the intestinal mucosal structure was preserved in the octreotide-treated group. In addition, treatment with octreotide significantly increased HO-1 expression and decreased NF-,B expression by immunohistochemistry when compared to the TNBS-induced colitis group. Conclusion:, Octreotide appears to have protective effects against colonic damage in TNBS-induced colitis. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression. [source] Association between activation of atypical NF-,B1 p105 signaling pathway and nuclear ,-catenin accumulation in colorectal carcinomaMOLECULAR CARCINOGENESIS, Issue 2 2010Johannes C. Lauscher Abstract Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to ,-catenin signaling leads to the stabilization of ,-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of I,B, and activation of canonical nuclear factor-,B (NF-,B) pathway. Here, we show that the noncanonical NF-,B1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with ,-catenin-mediated increased expression of CRD-BP and ,-TrCP1. In the carcinoma tissues exhibiting high levels of nuclear ,-catenin the phospho-p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF-,B pathway. Knockdown of CRD-BP in colorectal cancer cell line SW620 resulted in significantly higher basal levels of both NF-,B inhibitory proteins, p105 and I,B,. Furthermore decreased NF-,B binding activity was observed in CRD-BP siRNA-transfected SW620 cells as compared with those transfected with control siRNA. Altogether, our findings suggest that activation of NF-,B1 p105 signaling in colorectal carcinoma might be attributed to ,-catenin-mediated induction of CRD-BP and ,-TrCP1. © 2009 Wiley-Liss, Inc. [source] Induction of IL-10+ CD4+ CD25+ regulatory T cells with decreased NF-,B expression during immunotherapyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010Yi-Giien Tsai Tsai Y-G, Chiou Y-L, Chien J-W, Wu H-P, Lin C-Y. Induction of IL-10+ CD4+ CD25+ regulatory T cells with decreased NF-,B expression during immunotherapy. Pediatr Allergy Immunol 2010: 21: e166,e173. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard MyD88 is a major toll-like receptor (TLR) adaptor to activate NF-,B, which acts as a mater switch for allergic inflammation disease. Sterile hust dust extracts have been reported with TLR-dependent immunostimulatory activities. The aim of this study was to evaluate whether Dermatophagoides pteronyssinus (Der p) immunotherapy may increase IL-10+ CD4+ CD25+ T cells with modulating MyD88 signaling proteins, to decrease NF-,B expression. Peripheral blood mononuclear cells were isolated from patients before and after 1 yr of Der p immunotherapy, and also from matched control subjects. After 2 days of Der p-2 stimulation, intracellular IL-10 and Foxp3 expression of CD4+ CD25+ T cells were measured by flow-cytometry. The expression of IL-1 receptor-associated kinase (IRAK)-1 in cytoplasm and IFN-regulator factor-3 (IRF-3) with NF-,B/p65 in nuclei was determined by Western-blot analysis. Patients undergoing immunotherapy produced more soluble CD14, IL-10, and TGF-, that correlated with FEV1improvement (p < 0.05). In the immunotherapy group, the number of Foxp3+ CD4+ Treg cells increased more than the baseline status (25.06 ± 4.19 vs. 16.08 ± 3.54, p < 0.05). Additionally, increased IL-10 production with decreased IRAK-1 and NF-,B/p65 nuclear translocation was observed in sorted-purified Treg cells. IL-10+ CD4+ CD25+ Treg cells may respond to Der p-2 and down-regulate NF-,B/p65 expression to maintain immune tolerance during immunotherapy. [source] Cilostazol enhances apoptosis of synovial cells from rheumatoid arthritis patients with inhibition of cytokine formation via Nrf2-linked heme oxygenase 1 inductionARTHRITIS & RHEUMATISM, Issue 3 2010So Youn Park Objective To assess the effects of cilostazol in inhibiting proliferation and enhancing apoptosis in synovial cells from patients with rheumatoid arthritis (RA). Methods Synovial cell proliferation was measured by MTT assay. The expression of NF-,B, I,B,, Bcl-2, Bax, heme oxygenase 1 (HO-1), and Nrf2 was determined by Western blotting. Results Cilostazol suppressed synovial cell proliferation by arresting the G2/M phases of the cell cycle, and this was reversed by KT5720, an inhibitor of protein kinase A. Cilostazol increased the number of TUNEL-positive cells, with increased cytochrome c release and apoptosis-inducing factor translocation as well as increased caspase 3 activation. Cilostazol (10 ,M) and cobalt protoporphyrin IX (CoPP) increased HO-1 messenger RNA and protein expression. These effects were suppressed by zinc protoporphyrin IX (ZnPP), an HO-1 inhibitor. Cilostazol and CoPP significantly increased I,B, in the cytosol and decreased NF-,B p65 expression in the nucleus. Increased expression of tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), and IL-6 induced by lipopolysaccharide was attenuated by cilostazol and CoPP, and this was reversed by ZnPP. In mice with collagen-induced arthritis treated with cilostazol (10 and 30 mg/kg/day), paw thickness was decreased with increased apoptotic cells in the joints. In synovial cells transfected with small interfering RNA (siRNA) targeting HO-1, cilostazol did not suppress expression of TNF,, IL-1,, and IL-6, in contrast to findings with negative control cells. Cilostazol- and CoPP-induced HO-1 expression was diminished in cells transfected with Nrf2 siRNA. Conclusion Cilostazol suppressed proliferation of synovial cells from RA patients by enhancing apoptosis, and also inhibited cytokine production via mediation of cAMP-dependent protein kinase activation,coupled Nrf2-linked HO-1 expression. [source] | ||||||||||