title: Lactobacillus helveticus SBT2171 inhibits lymphocyte proliferation by regulation of the JNK signaling pathway.
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.
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hosoya
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sakai
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Shiozaki
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Endo
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ukibe
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uenishi
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kadooka
authors.affiliation: Milk Science Research Institute, Megmilk Snow Brand Co. LTD., Saitama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D052198:Lactobacillus helveticus / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D061251:Primary Cell Culture; D019936:Probiotics / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D016203:CDC2 Protein Kinase; D048670:MAP Kinase Kinase 4