PT  - JOURNAL ARTICLE
AU  - Mitsuyama, K
AU  - Matsumoto, S
AU  - Rose-John, S
AU  - Suzuki, A
AU  - Hara, T
AU  - Tomiyasu, N
AU  - Handa, K
AU  - Tsuruta, O
AU  - Funabashi, H
AU  - Scheller, J
AU  - Toyonaga, A
AU  - Sata, M
TI  - STAT3 activation via interleukin 6 trans-signalling contributes to ileitis in SAMP1/Yit mice
AID  - 10.1136/gut.2005.079343
DP  - 2006 Sep 01
TA  - Gut
PG  - 1263--1269
VI  - 55
IP  - 9
4099  - http://gut.bmj.com/content/55/9/1263.short
4100  - http://gut.bmj.com/content/55/9/1263.full
SO  - Gut2006 Sep 01; 55
AB  - Background and aim: SAMP1/Yit mice spontaneously develops intestinal inflammation. Previously, we demonstrated that the signal transducer and activator of transcription (STAT)-3/suppressor of cytokine signalling (SOCS)-3 pathway is pivotal in human inflammatory bowel disease. In our studies in SAMP1/Yit mice, the aim was to investigate whether STAT3 activation contributes to ileitis and to examine the therapeutic effects of this signal blockade. Methods: Intestinal expression of phospho-STAT3 in SAMP1/Yit mice and control AKR/J mice was examined by western blotting and immunohistochemistry. SOCS3 and interleukin 6 (IL-6) mRNA were determined by northern blotting and reverse transcription-polymerase chain reaction, respectively. We also examined the effects of intravenously injected hyper-IL-6, an IL-6/soluble IL-6 receptor fusion protein, and of soluble gp130-Fc, a specific inhibitor of soluble IL-6 receptor signalling, on STAT3 phosphorylation and disease severity in SAMP1/Yit mice. Results: Phospho-STAT3 was expressed strongly during the disease course in SAMP1/Yit mice but only transiently in AKR/J mice. Phospho-STAT3 was localised to epithelial and mononuclear cells in the diseased intestine of SAMP1/Yit mice. SOCS3 as well as IL-6 mRNAs were expressed in affected intestine. Administration of hyper-IL-6 caused disease exacerbation and enhancement of STAT3 phosphorylation. In contrast, soluble gp130-Fc administration ameliorated the disease and suppressed STAT3 phosphorylation. Conclusion: STAT3 signalling is critical in the development of intestinal inflammation in SAMP1/Yit mice. Blockade of this signalling pathway by soluble gp130-Fc may have therapeutic effects in inflammatory bowel disease.