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The neuropeptide α-melanocyte-stimulating hormone (α- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because α-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes α-MSH (L. casei-α-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the α-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and α-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-α-MSH on the colitis, L. casei or L. casei-α-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-α-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45±0. 2 g; L. casei-α- MSH: 18.2±0.12 g), colitis score (DSS alone: 3.6±0.4; L. casei-α-MSH: 1.4±0.6), MPO activity (DSS alone: 42.7±4.5 U/g; L. casei-α-MSH: 10.25±0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-α-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-κB activation. The α-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

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