抄録
In intestinal smooth muscle (SM), gastrointestinal (GI) inflammation induced motility disorder. However, possible mechanisms to induce GI dysmotility are not well understood. We here propound that inflammatory cytokines, IL-1β and TNF-α induce motility disorder of intestinal SM by altering contractile machinery in vitro and in vivo. In the organ cultured ileal SM tissue, IL-1β or TNF-α significantly inhibited carbachol-induced contraction in accompanied with decrease in MLC-phosphorylation. In the western blot analysis for detecting contractile proteins, only CPI-17 expression was significantly decreased by those cytokines treatment. In the series of experiments using IL-1αβ or TNF-α deficient mice, IL-1β did not induce down-regulation of CPI-17 expression in the organ cultured ileal tissue isolated from TNF-α deficient mice, indicating that IL-1β down-regulates CPI-17 expression via TNF-α production. In ileitis model induced by hapten, carbachol-induced contraction in the inflamed intestine was gradually inhibited with decrease in CPI-17 protein content within 2-3 days after the inflammation. This phenomenon could not detect in the ileitis model by using TNF-α deficient mice. In conclusion, we found that TNF-α directly affects on SM to induce impairment of Ca sensitization via down-regulation of CPI-17 expression. We concluded that CPI-17 is one of key molecules to induce motility disorder during GI inflammation. [J Physiol Sci. 2008;58 Suppl:S31]
