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P017. Th2 cytokines and cAMP mediated induction of SOCS3 expression in inactive ulcerative colitis

Y. Li, C. de Haar, C.J. van der Woude, E.J. Kuipers

Erasmus Medical Center, Rotterdam, The Netherlands

Background: The IL-6/STAT3 signaling plays an important role in intestinal homeostasis. SOCS3 is an important downstream negative-feedback target gene of the IL-6/STAT3 signal transduction pathway. We have recently shown that SOCS3 is expressed in the colonic epithelium of UC patients with inactive disease, while there were no signs of STAT3-phosphorylation (p-STAT3) in these epithelial cells. The lack of proper IL-6/STAT3 signaling could increase the vulnerability of the epithelial cells to inflammation induced damage, as previously shown in IL-6 Knockout mice.

Aim: Here we investigated the STAT3 independent induction of SOCS3 in intestinal epithelial cells.

Materials and methods: Colon epithelial cell line caco-2 were cultured with substances stimulating either p-STAT6 (Th2 cytokines IL-4/IL-13) or cAMP (PGE2/Forskolin) pathways, both of which have been associated with SOCS3 expression. The effect on SOCS3 expression was measured by quantitive-PCR (QPCR) and western blot (WB). In addition the expression of p-STAT6 and cAMP induced PKA-Cr were studied immunohistochemically in biopsies from inactive UC and healthy controls.

Results: Stimulation with either Th2 cytokines IL-4 and IL-13, or the cAMP inducers PGE2 and forskolin, increased the expression of SOCS3 at both mRNA and protein level. No p-STAT3 expression was detected after these stimulation. Biopsies from patients with inactive UC (expressing SOCS3) showed increased expression of p-STAT6 (p < 0.0001) and PKA-Cr (p = 0.0002) compared to healthy controls.

Conclusions: Our data provide evidence that Th2 cytokines and cAMP activation may be involved in the p-STAT3 independent SOCS3 expression detected in inactive UC biopsies.