title: Lipoteichoic acid-induced nitric oxide production depends on the activation of platelet-activating factor receptor and Jak2.
abstract: NO production by macrophages in response to lipoteichoic acid (LTA) and a synthetic lipopeptide (Pam3CSK4) was investigated. LTA and Pam3CSK4 induced the production of both TNF-alpha and NO. Inhibitors of platelet-activating factor receptor (PAFR) blocked LTA- or Pam3CSK4-induced production of NO but not TNF-alpha. Jak2 tyrosine kinase inhibition blocked LTA-induced production of NO but not TNF-alpha. PAFR inhibition blocked phosphorylation of Jak2 and STAT1, a key factor for expressing inducible NO synthase. In addition, LTA did not induce IFN-beta expression, and p38 mitogen-activated protein serine kinase was necessary for LTA-induced NO production but not for TNF-alpha production. These findings suggest that Gram-positive bacteria induce NO production using a PAFR signaling pathway to activate STAT1 via Jak2. This PAFR/Jak2/STAT1 signaling pathway resembles the IFN-beta, type I IFNR/Jak/STAT1 pathway described for LPS. Consequently, Gram-positive and Gram-negative bacteria appear to have different but analogous mechanisms for NO production.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
authors.forename: Je Hak
authors.initials: JH
authors.lastname: Kim
authors.forename: Ho Seong
authors.initials: HS
authors.lastname: Seo
authors.forename: Michael H
authors.initials: MH
authors.lastname: Martin
authors.forename: Gook-Hyun
authors.initials: GH
authors.lastname: Chung
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Michalek
authors.forename: Moon H
authors.initials: MH
authors.lastname: Nahm
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D053614:Janus Kinase 2; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D010455:Peptides / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D050794:STAT1 Transcription Factor; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D009569:Nitric Oxide; C009900:lipoteichoic acid; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2