RRC ID 34464
Author Hosoya T, Sakai F, Yamashita M, Shiozaki T, Endo T, Ukibe K, Uenishi H, Kadooka Y, Moriya T, Nakagawa H, Nakayama Y, Miyazaki T.
Title Lactobacillus helveticus SBT2171 inhibits lymphocyte proliferation by regulation of the JNK signaling pathway.
Journal PLoS One
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.
Volume 9(9)
Pages e108360
Published 2014-1-1
DOI 10.1371/journal.pone.0108360
PII PONE-D-14-15104
PMID 25268890
PMC PMC4182466
MeSH Animals Arthritis, Experimental / drug therapy* Arthritis, Experimental / genetics Arthritis, Experimental / metabolism Arthritis, Experimental / pathology B-Lymphocytes / drug effects* B-Lymphocytes / metabolism B-Lymphocytes / pathology CDC2 Protein Kinase / antagonists & inhibitors CDC2 Protein Kinase / genetics CDC2 Protein Kinase / metabolism Cell Line, Tumor Cell Proliferation / drug effects G2 Phase Cell Cycle Checkpoints / drug effects Gene Expression Regulation Humans Lactobacillus helveticus / physiology* Lymphocyte Activation / drug effects MAP Kinase Kinase 4 / antagonists & inhibitors MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism Male Mice Mice, Inbred C57BL Mice, Inbred DBA Primary Cell Culture Probiotics / pharmacology* Signal Transduction / drug effects T-Lymphocytes / drug effects* T-Lymphocytes / metabolism T-Lymphocytes / pathology
IF 2.74
Times Cited 17
General Microbes JCM 1120 JCM 1131