Lipoteichoic acid-induced nitric oxide production depends on the activation of platelet-activating factor receptor and Jak2

Academic Article


  • 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-α and NO. Inhibitors of platelet-activating factor receptor (PAFR) blocked LTA- or Pam3CSK4-induced production of NO but not TNF-α. Jak2 tyrosine kinase inhibition blocked LTA-induced production of NO but not TNF-α. PAFR inhibition blocked phosphorylation of Jak2 and STAT1, a key factor for expressing inducible NO synthase. In addition, LTA did not induce IFN-β expression, and p38 mitogen-activated protein serine kinase was necessary for LTA-induced NO production but not for TNF-α 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-β, 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. Copyright © 2005 by The American Association of Immunologists, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Han SH; Kim JH; Seo HS; Martin MH; Chung GH; Michalek SM; Nahm MH
  • Start Page

  • 573
  • End Page

  • 579
  • Volume

  • 176
  • Issue

  • 1