Enzymatically triggered self-assembly of poly(ethylene glycol)-attached oligopeptides into well-organized nanofibers.

A unique and programmable peptide self-assembling system has been fabricated by using poly(ethylene glycol)-attached amphiphilic oligopeptide, which shows rapid self-assembly into well-organized beta-sheet nanofibers in response to an enzymatic reaction.

Butyrate blocks interferon-gamma-inducible protein-10 release in human intestinal subepithelial myofibroblasts.

BACKGROUND: Interferon (IFN)-gamma-inducible protein (IP)-10 is a chemoattractant for CXCR 3-expressing T lymphocytes and monocytes. IP-10 has been reported to mediate chronic inflammation such as that in inflammatory bowel disease (IBD). However, the local secretion of IP-10 in the intestine remains unclear. In this study, we investigated IP-10 secretion in human colonic subepithelial myofibroblasts (SEMFs). METHODS: IP-10 secretion was determined by enzyme-linked immunosorbent assay (ELISA), and IP-10 mRNA expression was evaluated by Northern blotting. RESULTS: Interleukin (IL)-10 mRNA was not detected in unstimulated SEMFs. Interferon (IFN)-gamma strongly induced IP-10 mRNA expression. Tumor necrosis factor (TNF)-alpha also stimulated IP-10 mRNA expression, but this was much weaker than that induced by IFN-gamma. The effects of IFN-gamma and TNF-alpha were detected in a dose- and time-dependent manner. These responses were also observed at the protein levels. The IFN-gamma-induced IP-10 secretion was not affected by acetate or propionate, but was significantly reduced by butyrate. Trichostatin A, a specific inhibitor of histone deacetylase, also blocked the IFN-gamma- and TNF-alpha-induced IP-10 mRNA expression, but the effects of trichostatin A were weaker than those of butyrate. The inhibitory effect of butyrate on IFN-gamma-induced IP-10 release was not associated with STAT (signaling transducer and activator of transcription)-1alpha activation. CONCLUSIONS: We demonstrated that human colonic SEMFs are the local site for the secretion IP-10. The regulation of IP-10 release by IFN-gamma and butyrate may play an important role in controlling chronic mucosal inflammation in pathological entities such as IBD.

Suppression of interleukin-1beta- and tumor necrosis factor-alpha-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis.

BACKGROUND: To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we investigated the alterations in the cytokine responses of peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in ulcerative colitis (UC) patients. METHODS: Twelve patients with UC who did not respond to steroid therapy were enrolled. Nine patients responded to LCAP therapy, but 3 patients did not show clinical improvement. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first and second session of LCAP treatment. Cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the levels of secreted IL-8 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: LCAP induced a significant decrease in peripheral lymphocyte, monocyte, and platelet counts. IL-1beta- and TNF-alpha-induced IL-8 and IL-6 secretion was significantly decreased after the first and second LCAP treatments. These responses were associated with inhibitory effects on nuclear factor (NF)-kappaB DNA-binding activity. CONCLUSIONS: LCAP downregulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMCs isolated from UC patients. The induction of hyporesponsiveness to proinflammatory cytokines may be an important factor mediating the clinical effects of LCAP in UC patients.