IL-6/STAT-3 signals play key roles in
inflammatory bowel disease (IBD). It is known that Lactobacillus casei strain Shirota (LcS) improves inflammatory disorders. This study aimed to elucidate the effect of LcS on murine chronic IBD and to clarify the mechanism. We focused the inhibitory effect of LcS on the production of
IL-6 in
lipopolysaccharide (LPS)-stimulated large intestinal lamina propria mononuclear cells (LI-LPMC) isolated from mice with chronic
colitis and in RAW264.7 cells in vitro. We also determined in vivo the effect of LcS on murine chronic IBD models induced with
dextran sodium sulphate and SAMP1/Yit mice. Finally, we examined the cellular determinants of LcS for the down-regulation of
IL-6 secretion by LI-LPMC, RAW264.7 cells and peripheral blood mononuclear cells (PBMC) derived from patients with
ulcerative colitis (UC). LcS, but not other strains of Lactobacillus, inhibited the production of
IL-6 in LPS-stimulated LI-LPMC and RAW264.7 cells, down-regulating the nuclear translocation of
NF-kappaB. The LcS-diet-improved murine chronic
colitis is associated with the reduction of
IL-6 synthesis by LI-LPMC. LcS also improved chronic
ileitis in SAMP1/Yit mice. The release of
IL-6 in vitro in LPS-stimulated LI-LPMC, RAW 264.7 cells and UC-PBMC was inhibited by a
polysaccharide-
peptidoglycan complex (PSPG) derived from LcS. This probiotic-induced improvement in murine chronic
inflammatory bowel disease is associated with the down-regulation of pro-inflammatory
cytokines such as
IL-6 and IFN-gamma production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human
inflammatory bowel disease.