Lactobacillus casei Secreting α-MSH Induces the Therapeutic Effect on DSS-Induced Acute Colitis in Balb/c Mice

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-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 alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-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-alpha-MSH on the colitis, L. casei or L. casei-alpha-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-a-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45 +/- 0. 2 g; L. casei-alpha-MSH: 18.2 +/- 0.12 g), colitis score (DSS alone: 3.6 +/- 0.4; L. casei-alpha-MSH: 1.4 +/- 0.6), MPO activity (DSS alone: 42.7 +/- 4.5 U/g; L. casei-alpha-MSH: 10.25 +/- 0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappa B activation. The alpha-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.