title: Induction of necrosis factor-alpha and interleukin-6 in mice in vivo and in murine peritoneal macrophages and human whole blood cells in vitro by Micrococcus luteus teichuronic acids.
abstract: Earlier studies showed that Micrococcus luteus cells and cell walls induced anaphylactoid reactions leading to death, in some instances within 1 h, in C3H/HeN mice primed with muramyl dipeptide (MDP). They also induced serum cytokines in the surviving mice. The present study investigated the structural components responsible for these activities. Teichuronic acids, a component of M. luteus cell walls, induced tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in MDP-primed C3H/HeN mice. Peptidoglycans had little effect on the cytokine-inducing activities. Reducing teichuronic acids, i.e., teichuronic acids whose carboxyl groups had been reduced, lost their cytokine-inducing activities. Neither peptidoglycans nor teichuronic acids induced anaphylactoid reactions in the MDP-primed mice. Purified teichuronic acids also induced TNF-alpha and IL-6 production in C3H/HeN murine peritoneal macrophages and human whole-blood cells in the culture, but reduced teichuronic acids did not. The purified teichuronic acids induced no TNF-alpha and only low levels of IL-6 in MDP-primed C3H/HeJ mice, and neither cytokine in peritoneal macrophage cultures from C3H/HeJ mice with a single point of mutation in Toll-like receptor 4 (TLR4) gene. These findings suggest that induction of cytokines by teichuronic acids is mainly TLR4-dependent.
authors.forename: T
authors.initials: T
authors.lastname: Monodane
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima 890-8544, *Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575 and †Department of Chemistry, Graduate School of Science, Osaka University, Toyonka 560-0043, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabata
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima 890-8544, *Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575 and †Department of Chemistry, Graduate School of Science, Osaka University, Toyonka 560-0043, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima 890-8544, *Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575 and †Department of Chemistry, Graduate School of Science, Osaka University, Toyonka 560-0043, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hase
authors.affiliation: Department of Microbiology and Immunology, Kagoshima University Dental School, Kagoshima 890-8544, *Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575 and †Department of Chemistry, Graduate School of Science, Osaka University, Toyonka 560-0043, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takada
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000707:Anaphylaxis / Q000209:etiology*; D000818:Animals; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016982:Micrococcus luteus / Q000276:immunology / Q000378:metabolism*; D010457:Peptidoglycan / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014574:Uronic Acids / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D010457:Peptidoglycan; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D014574:Uronic Acids; C010788:teichuronic acid; D000119:Acetylmuramyl-Alanyl-Isoglutamine