Перегляд вихідного коду сторінки H2 cytokine production. Other people have observed increased mucosal expression of the

In contrast to our findings with oxazolone colitis, [https://www.medchemexpress.com/PCI-32765.html Ibrutinib biological activity] others observed exacerbation of acute dextran sulfate sodium (DSS)-induced colitis in STAT6-/- mice (30). In reality, DSS colitis doesn't demand T cells because it occurs in serious combined immunodeficient BALB/c mice (33). Inside the IL-4-dependent TCR-/- model of colitis, Okuda et al. found no effect of STAT6 genetic deletion on colitis development, supporting a role 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 entirely prevented in STAT6-/- OXA mice. Within a mouse coinfection model with the helminth Heligmosomoides polygyrus and also the Gram-negative bacterium Citrobacter rodentium, STAT6-/- mice exhibited much less intestinal inflammation [https://dx.doi.org/10.1038/srep32673 title= srep32673] in association with reduced infiltration of colonic lamina propria alternatively activated macrophages (35). Altered tight junction [https://dx.doi.org/10.2147/CEG.S111693 title= CEG.S111693] structure and impaired epithelial barrier function is usually a hallmark of the diseased mucosa in UC (36). IL-13, that is upregulated in UC, impairs colon epithelial cell permeability in vitro by inducing expression claudin-2, which can be also elevated in the mucosa of UC sufferers (six, 23, 37, 38). The present study could be the 1st demonstration of induction of epithelial claudin-2 in oxazolone colitis, [https://dx.doi.org/10.7554/eLife.14985 title= eLife.14985] and that oxazolone-induced claudin-2 is STAT6-dependent. This observation is in line with all the findings of other groups that have demonstrated within the tiny intestine that in vivo IL-13-induced barrier dysfunction is STAT6 dependent (39, 40). Other individuals and we have 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). Here, we demonstrate a partial abrogation on the IL-13mediated TER lower in T84 cells with steady knockdown of STAT6 expression, that is in line with findings by Wu et al. in CaCo2bbe cells (39). In contrast, others have observed that IL-13 regulation of epithelial permeability was not STAT6-dependen.H2 cytokine production. Others 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 of your receptor in both colon tissue and MLN cells from these mice and identified 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 an important function for STAT6 in the pathogenesis of oxazolone colitis, a murine model with phenotypic and immunologic similarities to human UC. In association with reduced colitis severity, STAT6-/- mice demonstrate reduced epithelial claudin-2 expression, reduced tissue mRNA expression with the Th2-inducing cytokines IL-33 and TSLP, and lowered MLN cell proinflammatory cytokine secretion. The existing literature reveals varying contributions of STAT6 to intestinal inflammation according to the model studied. In contrast to our findings with oxazolone colitis, other folks observed exacerbation of acute dextran sulfate sodium (DSS)-induced colitis in STAT6-/- mice (30).