title: CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9.
abstract: We previously reported the strong immunostimulatory effects of a CpG oligodeoxynucleotide (ODN), designated MsST, from the lacZ gene of Streptococcus (S.) thermophilus ATCC19258. Here we show that 24h of stimulation with MsST in mouse splenocytes and peritoneal macrophages strongly induces expression of interleukin (IL)-33, a cytokine in the IL-1 superfamily. Other IL-1 superfamily members, including IL-1alpha, IL-1beta and IL-18, are down-regulated after 24h of stimulation of MsST. We also found that MsST-induced IL-33 mRNA expression is inhibited by the suppressive ODN A151, which can inhibit Toll-like receptor 9 (TLR9)-mediated responses. This is the first report to show that IL-33 can be induced by CpG ODNs. The strong induction of IL-33 by MsST suggests that it may be a potential therapeutic ODN for the treatment of inflammatory disease. The presence of a strong CpG ODN in S. thermophilus also suggests that the bacterium may be a good candidate as a starter culture for the development of new physiologically functional foods.
authors.affiliation: Fiber-Nanotech Young Researcher Empowerment Center, Shinshu University, Minamiminowa 399-4598, Japan. shimot@shinshu-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimosato
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Tohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Mariko
authors.initials: M
authors.lastname: Tateo
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology*; D056747:Immunomodulation; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis*; D007763:Lac Operon / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D048249:Streptococcus thermophilus / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C506535:Il33 protein, mouse; D007155:Immunologic Factors; D000067596:Interleukin-33; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D001616:beta-Galactosidase