In this study, we investigated the contribution of complement to

In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression

of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene CH5183284 sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (-2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with

decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD. Laboratory Investigation (2011) 91, 472-483; doi:10.1038/labinvest.2010.183; Nutlin-3a nmr published online 22 November 2010″
“Metabotropic Selleckchem ��-Nicotinamide glutamate receptors (mGluRs) regulate neurogenesis in brain, but the mechanisms remain unknown. In this study, we investigated the effect of mGluR5 on the proliferation of human embryonic neural stem/progenitor cells

(NPCs), the expression of cyclin D1 and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that mGluR5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) increased the proliferation of NPCs by increasing cell activity, diameter of neurospheres and cell division, while mGluR5 siRNA and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP) decreased the NPC proliferation. The mRNA and protein expressions of cyclin D1 increased with DHPG treatment and decreased after siRNA or MPEP treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal protein kinase (JNK) signaling pathways were involved in the proliferation of NPCs. After DHPG treatment, p-ERK1/2 and p-JNK2 levels increased, and meanwhile p-p38 level decreased; but p-ERK1/2 and p-JNK2 levels decreased after siRNA or MPEP treatment, and p-p38 level increased.

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