Lipoteichoic acid-induced nitric oxide production depends on the activation of platelet-activating factor receptor and Jak2.
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.
Han
Seung Hyun
SH
Department of Pathology, University of Alabama at Birmingham, AL 35294, USA.
Kim
Je Hak
JH
Seo
Ho Seong
HS
Martin
Michael H
MH
Chung
Gook-Hyun
GH
Michalek
Suzanne M
SM
Nahm
Moon H
MH
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
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