Inflammatory bowel disease (IBD) represents a group of chronic inflammatory diseases characterized by inflammation and relapsing gastrointestinal disorders. Recent studies have shown that Th17 cells, which are well known as key mediators of chronic inflammation, have a pivotal role in onset and development of IBD in humans and mice, alike. In recent years, it has been reported that IL-27, which is an IL-12-related heterodimeric cytokine consisting of EBI3 and p28 subunits, act directly on naive T cells to suppress the differentiation of Th17 cells. However, effects of exogenous IL-27 on the IBD are not well elucidated. To clarify the suppressive effect of IL-27 treatment on IBD, we applied the flexible linking method to EBI3 and p28 subunits and generated a single-chain human IL-27 (scIL-27). scIL-27 inhibited xenogenic mouse Th17 cell differentiation in vitro, indicating that scIL-27 also acts in mouse immune systems. In a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse acute colitis model, subcutaneous scIL-27 treatment significantly improved the colon length, extent of necrosis, and ulceration and thickened epithelium and several pathological scores in a dose-dependent manner. scIL-27 clearly suppressed several inflammatory cytokines, including IL-17, in inflamed colon, except for anti-inflammatory cytokine IL-10. The mesenteric lymph node cells from scIL-27-treated mice also exhibited a reduced inflammatory response and, furthermore, a lower population of Th17 cells than those of PBS-treated mice. Finally, we showed the therapeutic efficacy of scIL-27 on TNBS-induced colitis even after active colitis was established. These results suggest new possible therapeutic approaches for IBD, including disorders such as Crohn's disease and ulcerative colitis.
Polarized Raman scattering experiments on misfit layer compounds (RShTaSz (R e La, Ce, Sm or Gd; S = sulphur; x z 1.2) have been carried out in order IO investigate the effect of the charge transfer (n) from an RS layer to a TaSz layer on the vibrational motion. ?%e mode assignment is made by comparing the spectra of (RS),TaSz with those of ZH-TaS2 and (RS),NbSz. The modes at frequencies below about 200 cm-' are ascribed to the intralayer modes of the RS layer and the main peaks higher than 2W cm-' are ascribed to the intralayer modes of the TaS2 layer. The E mode relevant to the TaSl layer shiffs upwards by about 40 cm-' relative to the corresponding mode in 2H-Ta.52 while the A mode hardly shiRs. In addition to the inMlayer modes of each layer, extra modes which show an misotmpy in the basal plane are observed at 360-370 em-'. These observntions indicate that the restoring forces for intralayer and interlayer interactions strengthen owing to the CT. The two-phonon Raman band is observed at higher frequencies than that of 2H-TaSa~2. The comparison with the spectra of (RS),NbSz shows lhat the amount of the CT in (RShTaSz is less than that in (RShNbS2.
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