摘要

This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-κB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IκB-α phosphorylation and IκB-α degradation in the cytosol, and translocation of p65 and p50 NF-κB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-κB activation by detecting the formation of NF-κB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-κB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.
原文英語
頁(從 - 到)136-145
頁數10
期刊Journal of Biomedical Science
10
發行號1
DOIs
出版狀態已發佈 - 2003

指紋

Macrophages
Nitric Oxide Synthase
Protein Kinase C
Staphylococcus aureus
Type C Phospholipases
Nitric Oxide Synthase Type II
Nitric Oxide
Chemical activation
Myristic Acid
Tetradecanoylphorbol Acetate
Phosphatidylinositols
Phosphatidylcholines
Cytosol
Acetates
Cells
Phosphorylation
lipoteichoic acid
Ketones
Degradation
DNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

引用此文

@article{5df0359314324a5c9b77995ad22ba9ec,
title = "Induction of nitric oxide synthase in RAW 264.7 macrophages by lipoteichoic acid from Staphylococcus aureus: Involvement of protein kinase C- and nuclear factor-κB-dependent mechanisms",
abstract = "This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-κB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IκB-α phosphorylation and IκB-α degradation in the cytosol, and translocation of p65 and p50 NF-κB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-κB activation by detecting the formation of NF-κB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-κB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.",
keywords = "Inducible nitric oxide synthase, Lipoteichoic acid, NF-κB, Nitric oxide, Protein kinase C, RAW 264.7 macrophages",
author = "Kuo, {Chen Tzu} and Chiang, {Ling Ling} and Chun-Nin Lee and Yu, {Ming Chih} and Bai, {Kuan Jen} and Lee, {Horng Mo} and Lee, {Wen Sen} and Sheu, {Joen Rong} and Lin, {Chien Huang}",
year = "2003",
doi = "10.1159/000068076",
language = "English",
volume = "10",
pages = "136--145",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Induction of nitric oxide synthase in RAW 264.7 macrophages by lipoteichoic acid from Staphylococcus aureus

T2 - Involvement of protein kinase C- and nuclear factor-κB-dependent mechanisms

AU - Kuo, Chen Tzu

AU - Chiang, Ling Ling

AU - Lee, Chun-Nin

AU - Yu, Ming Chih

AU - Bai, Kuan Jen

AU - Lee, Horng Mo

AU - Lee, Wen Sen

AU - Sheu, Joen Rong

AU - Lin, Chien Huang

PY - 2003

Y1 - 2003

N2 - This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-κB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IκB-α phosphorylation and IκB-α degradation in the cytosol, and translocation of p65 and p50 NF-κB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-κB activation by detecting the formation of NF-κB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-κB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.

AB - This study investigates the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release caused by Staphylococcus aureus lipoteichoic acid (LTA) in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated LTA-induced iNOS expression and NO release. Two PKC inhibitors (Go 6976 and Ro 31-8220), an NF-κB inhibitor (pyrrolidine dithiocarbamate; PDTC), and long-term (24 h) 12-phorbol-13-myristate acetate (PMA) treatment each also inhibited LTA-induced iNOS expression and NO release. Treatment of cells with LTA caused an increase in PKC activity; this stimulatory effect was inhibited by D-609, U-73122, or Ro 31-8220. Stimulation of cells with LTA caused IκB-α phosphorylation and IκB-α degradation in the cytosol, and translocation of p65 and p50 NF-κB from the cytosol to the nucleus. Treatment of cells with LTA caused NF-κB activation by detecting the formation of NF-κB-specific DNA-protein complexes in the nucleus; this effect was inhibited by Go 6976, Ro 31-8220, long-term PMA treatment, PDTC, L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), and calpain inhibitor I. These results suggest that LTA might activate PC-PLC and PI-PLC to induce PKC activation, which in turn initiates NF-κB activation, and finally induces iNOS expression and NO release in RAW 264.7 macrophages.

KW - Inducible nitric oxide synthase

KW - Lipoteichoic acid

KW - NF-κB

KW - Nitric oxide

KW - Protein kinase C

KW - RAW 264.7 macrophages

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U2 - 10.1159/000068076

DO - 10.1159/000068076

M3 - Article

C2 - 12607534

AN - SCOPUS:0037256291

VL - 10

SP - 136

EP - 145

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

ER -