title: LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages.
abstract: BACKGROUND
  Lipoteichoic acid (LTA) and lipopolysaccharide (LPS), the toxicants from bacteria, are potent inducers of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1). Although LTA is much less reported than that on LPS, LTA is regarded as the gram-positive equivalent to LPS in some aspects. We investigated the LTA-induced signal transduction and biological effects, as well as to compare the effect of LTA with that of LPS.
  
  
  METHODS
  Kinase assay, ELISA and RT-PCR were performed to delineate LTA and LPS signaling as well as to determine the secretion and RNA expression of TNF and IL-1.
  
  
  RESULTS
  Src, Lyn and MAPKs are involved in LTA and LPS signaling in murine macrophages. Additionally, blockades of PKC, PI3K and p38, respectively, caused significant inhibition of both LTA- and LPS-induced proIL-1/IL-1 and TNF expression. ERK inactivation moderately reduced LTA- and LPS-induced proIL-1/IL-1, but considerably reduced TNF expression. Inhibition of JNK engendered super-induction of IL-1 secretion, but diminished TNF secretion. Strikingly, both IL-1 and TNF protein induction were declined by overexpression of dominant negative form of JNK.
  
  
  CONCLUSIONS
  The results clarify the similarity and difference between LTA- and LPS-mediated signal transduction and induction of inflammatory cytokines in macrophages.
authors.affiliation: Biotechnology and Laboratory Science in Medicine, Institute of Biotechnology in Medicine, National Yang-Ming University, 155 Li-Nong Street, Shih-Pai, Taipei 112, Taiwan.
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Louis Kuoping
authors.initials: LK
authors.lastname: Chao
authors.forename: Sai-Koong
authors.initials: SK
authors.lastname: Tan
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Hsien-Yeh
authors.initials: HY
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004925:Escherichia / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013289:Streptococcaceae / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D011494:Protein Kinases