Lactobacillus casei secreting alpha-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-alpha-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-kappaB 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.
Yoon
Sun-Woo
SW
Mucosal Immunology Laboratory, BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejon 305-600, Korea.
Lee
Chul-Ho
CH
Kim
Jeong-Yoon
JY
Kim
Jie-Youn
JY
Sung
Moon-Hee
MH
Poo
Haryoung
H
D000208:Acute Disease; D000818:Animals; D003001:Cloning, Molecular; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007378:Interleukins / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D007378:Interleukins; D016328:NF-kappa B; D000521:alpha-MSH; D016264:Dextran Sulfate