LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages.
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.
Su
Shih-Chi
SC
Biotechnology and Laboratory Science in Medicine, Institute of Biotechnology in Medicine, National Yang-Ming University, 155 Li-Nong Street, Shih-Pai, Taipei 112, Taiwan.
Hua
Kuo-Feng
KF
Lee
Hsinyu
H
Chao
Louis Kuoping
LK
Tan
Sai-Koong
SK
Lee
Hsinyu
H
Yang
Shun-Fa
SF
Hsu
Hsien-Yeh
HY
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
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D011494:Protein Kinases