Abstract
Lactobacillus helveticus SBT2171 (LH2171) is a lactic acid bacterium with high protease activity and used in starter cultures in the manufacture of cheese. We recently reported that consumption of cheese manufactured using LH2171 alleviated symptoms of dextran sodium sulfate (DSS)-induced colitis in mice. In this study, we have examined whether LH2171 itself exerts an inhibitory effect on the excessive proliferation of lymphocytes. We found that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB. Cell cycle analysis showed an accumulation of LH2171-treated BJAB cells in the G2/M phase. Further, phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun was reduced by LH2171 in BJAB cells. Subsequently, expression of cell division cycle 2 (CDC2), regulated by the JNK signaling pathway and essential for G2/M phase progression, was inhibited by LH2171. It was also demonstrated that intraperitoneal administration of LH2171 strongly alleviated symptoms of collagen-induced arthritis (CIA) in mice. These findings suggest that LH2171 inhibits the proliferation of lymphocytes through a suppression of the JNK signaling pathway and exerts an immunosuppressive effect in vivo.
Highlights
The immune system is normally maintained by a balance between protective immunity against pathogens and tolerance to self-antigens, and disruption to this balance arising from the abnormal activation and proliferation of lymphocytes causes autoimmune diseases associated with chronic inflammation such as rheumatoid arthritis (RA) or inflammatory bowel disease (IBD)
Lactobacillus helveticus SBT2171 (LH2171) inhibits the proliferation of lymphocytes To evaluate the in vitro immunosuppressive effect of LH2171, we examined the effect of LH2171 and two types of strains of Lactobacillus, L. helveticus JCM1120T (LH1120T) and Lactobacillus gasseri JCM1131T (LG1131T), on the proliferation of mouse splenocytes
The present study demonstrates that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB, in vitro
Summary
The immune system is normally maintained by a balance between protective immunity against pathogens and tolerance to self-antigens, and disruption to this balance arising from the abnormal activation and proliferation of lymphocytes causes autoimmune diseases associated with chronic inflammation such as rheumatoid arthritis (RA) or inflammatory bowel disease (IBD). Immunosuppressive agents that suppress excessive proliferation of lymphocytes act as therapeutic drugs for inflammatory autoimmune diseases. Some probiotic strains of LAB have been shown to contribute to the host immune homeostasis by modulating the innate and adaptive immune system [3]. Recent studies have shown that some strains of LAB and its components directly suppress the proliferation of lymphocytes in vitro [4,5,6]. In the process of activation and proliferation of lymphocytes, intracellular signaling pathways are mediated by mitogen-activated protein kinases (MAPKs) including the c-Jun N-terminal kinase (JNK) [7]. Whether LAB strains suppress these intracellular signaling pathways to inhibit the proliferation of lymphocytes remains unclear
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