title: The role of nucleotide-binding oligomerization domain 1 during cytokine production by macrophages in response to Mycobacterium tuberculosis infection.
abstract: Tuberculosis due to Mycobacterium tuberculosis infection is a leading cause of death worldwide. Recognition of this pathogen is crucial for the activation of innate and adaptive immune responses. Nucleotide-binding oligomerization domain (Nod)1 and Nod2 are cytoplasmic receptors that can detect unique muropeptides of bacterial peptidoglycan. Nod2 is critical for the initiation of the host immune response against M. tuberculosis infection, however the role of Nod1 remains largely unknown. We investigated the role of Nod1 with respect to cytokine production by bone marrow-derived macrophages (BMDMs) in response to M. tuberculosis infection. Production of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β were induced in BMDMs; cytokine levels were not affected by a deficiency in Nod1. Activation of NF-κB and MAPKs was also comparable between wild-type and Nod1-deficient BMDMs. Levels of IL-6 and IL-1β were reduced in Nod1/Nod2 double-deficient BMDMs to a greater extent than in Nod2-deficient cells. Furthermore, when signaling of Toll-like receptors (TLRs) was inhibited by lipopolysaccharide pre-treatment, cytokine production was diminished in Nod1-deficient BMDMs. Our results indicate that Nod1 cooperates with Nod2 or TLRs to produce cytokines in macrophages in response to M. tuberculosis infection.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Sang-Muk
authors.initials: SM
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University of Medicine, Seoul 129-740, Republic of Korea. Electronic address: sjshin@yuhs.ac.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: jonpark@jnu.ac.kr.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Cytokines; Innate immune response; Macrophages; Nod1