Відмінності між версіями «H2 cytokine production. Other individuals have observed increased mucosal expression in the»

Поточна версія на 08:10, 6 лютого 2018

In contrast, other individuals have observed that IL-13 regulation of epithelial permeability was not STAT6-dependen.H2 cytokine production. Other folks have observed elevated mucosal expression with the IL-33 receptor, ST2 in intestinal inflammation (29). We assessed mRNA expression for both the soluble (sST2) and membrane-bound (ST2L) isoforms with the receptor in both colon tissue and MLN cells from these mice and discovered no differences in expression of either isoform amongst WT ETOH, WT OXA, and STAT6-/- OXA mice (Supplemental Figure 1). TakenJ Immunol. Author manuscript; available in PMC 2014 February 15.Rosen et al.Pagetogether, IL-33 augments T cell proinflammatory Th2 and Th1 cytokine secretion, even in STAT6-/- mice.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDISCUSSIONIn the present study, we demonstrate a vital role for STAT6 in the pathogenesis of oxazolone colitis, a murine model with phenotypic and immunologic similarities to human UC. In association with decreased colitis severity, STAT6-/- mice demonstrate decreased epithelial claudin-2 expression, decreased tissue mRNA expression on the Th2-inducing cytokines IL-33 and TSLP, and decreased MLN cell proinflammatory cytokine secretion. The existing literature reveals varying contributions of STAT6 to intestinal inflammation depending on the model studied. In contrast to our findings with oxazolone colitis, others observed exacerbation of acute dextran sulfate sodium (DSS)-induced colitis in STAT6-/- mice (30). Even though Th2 inflammation has been implicated in chronic models of DSS colitis, acute DSS colitis has been connected predominantly with Th1 inflammation (31, 32). In truth, DSS colitis does not call for T cells because it happens in serious combined immunodeficient BALB/c mice (33). Within the IL-4-dependent TCR-/- model of colitis, Okuda et al. located no effect of STAT6 genetic deletion on colitis improvement, supporting a function for STAT6independent IL-4 signaling in intestinal inflammation and Th2 cell differentiation (34). Their findings are in line with our observations that tissue IL-13 expression persisted and colitis was not totally prevented in STAT6-/- OXA mice. Inside a mouse coinfection model using the helminth Heligmosomoides polygyrus as well as the Gram-negative bacterium Citrobacter rodentium, STAT6-/- mice exhibited less intestinal inflammation title= srep32673 in association with lowered infiltration of colonic lamina propria alternatively activated macrophages (35). Altered tight junction title= CEG.S111693 structure and impaired epithelial barrier function is a hallmark with the diseased mucosa in UC (36). IL-13, which is upregulated in UC, impairs colon epithelial cell permeability in vitro by inducing expression claudin-2, which can be also increased in the mucosa of UC individuals (6, 23, 37, 38). The present study could be the initial demonstration of induction of epithelial claudin-2 in oxazolone colitis, title= eLife.14985 and that oxazolone-induced claudin-2 is STAT6-dependent. This observation is in line together with the findings of other groups who've demonstrated within the PD150606 site little intestine that in vivo IL-13-induced barrier dysfunction is STAT6 dependent (39, 40). Other individuals and we've previously shown that, in vitro, IL-13-mediated reductions in TER are lessened with SAHA, a protein deacetylase inhibitor with STAT6 inhibitory properties (8, 23). Right here, we demonstrate a partial abrogation with the IL-13mediated TER reduce in T84 cells with stable knockdown of STAT6 expression, which is in line with findings by Wu et al. in CaCo2bbe cells (39).