Lipoteichoic acid induces nuclear factor-κB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages

Shang Jyh Kao, Hui Chieh Lei, Chen Tzu Kuo, Ming Shyan Chang, Bing Chang Chen, Yau Chong Chang, Wen Ta Chiu, Chien Huang Lin

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

We previously demonstrated that lipoteichoic acid (LTA) might activate phosphatidylcholine-phospholipase C (PC-PLC) and phosphatidylinositol- phospholipase C (PI-PLC) to induce protein kinase C activation, which in turn initiates nuclear factor-κB (NF-κB) activation and finally induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release in RAW 264.7 macrophages. In this study, we further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt, and p38 mitogen-activated protein kinase (MAPK) in LTA-induced iNOS expression and NO release in RAW 264.7 macrophages. Tyrosine kinase inhibitors (genistein and tyrphostin AG126), PI3K inhibitors (wortmannin and LY 294002), and a p38 MAPK inhibitor (SB 203580) attenuated LTA-induced iNOS expression and NO release in concentration-dependent manners. Treatment of RAW 264.7 macrophages with LTA caused time-dependent activations of Akt and p38 MAPK. The LTA-induced Akt activation was inhibited by wortmannin, LY 294002, genistein, and tyrphostin AG126. The LTA-induced p38 MAPK activation was inhibited by genistein, tyrphostin AG126, wortmannin, LY 294002, and SB 203580. The LTA-induced formation of an NF-κB-specific DNA-protein complex in the nucleus was inhibited by wortmannin, LY 294002, genistein, tyrphostin AG126, and SB 203580. Treatment of macrophages with LTA caused an increase in κB-luciferase activity, and this effect was inhibited by tyrphostin AG126, wortmannin, LY 294002, the Akt dominant negative mutant (AktDN), and SB 203580. Based on those findings, we suggest that LTA might activate the PI3K/Akt pathway through tyrosine kinase to induce p38 MAPK activation, which in turn initiates NF-κB activation, and ultimately induces iNOS expression and NO release in RAW 264.7 macrophages.

Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalImmunology
Volume115
Issue number3
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

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Phosphatidylinositol 3-Kinase
p38 Mitogen-Activated Protein Kinases
Nitric Oxide Synthase
Tyrphostins
Macrophages
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Genistein
Nitric Oxide Synthase Type II
1-Phosphatidylinositol 4-Kinase
Nitric Oxide
Protein-Tyrosine Kinases
Type C Phospholipases
lipoteichoic acid
Protein Kinase Inhibitors
Phosphatidylinositols
Luciferases
Phosphatidylcholines
Protein Kinase C
wortmannin
AG 127

Keywords

  • Inducible nitric oxide synthase
  • Lipoteichoic acid
  • NF-κB
  • Nitric oxide
  • p38 MAPK
  • PI3K
  • Raw 264.7 macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Lipoteichoic acid induces nuclear factor-κB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages. / Kao, Shang Jyh; Lei, Hui Chieh; Kuo, Chen Tzu; Chang, Ming Shyan; Chen, Bing Chang; Chang, Yau Chong; Chiu, Wen Ta; Lin, Chien Huang.

In: Immunology, Vol. 115, No. 3, 07.2005, p. 366-374.

Research output: Contribution to journalArticle

Kao, Shang Jyh ; Lei, Hui Chieh ; Kuo, Chen Tzu ; Chang, Ming Shyan ; Chen, Bing Chang ; Chang, Yau Chong ; Chiu, Wen Ta ; Lin, Chien Huang. / Lipoteichoic acid induces nuclear factor-κB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages. In: Immunology. 2005 ; Vol. 115, No. 3. pp. 366-374.
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AU - Kao, Shang Jyh

AU - Lei, Hui Chieh

AU - Kuo, Chen Tzu

AU - Chang, Ming Shyan

AU - Chen, Bing Chang

AU - Chang, Yau Chong

AU - Chiu, Wen Ta

AU - Lin, Chien Huang

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N2 - We previously demonstrated that lipoteichoic acid (LTA) might activate phosphatidylcholine-phospholipase C (PC-PLC) and phosphatidylinositol- phospholipase C (PI-PLC) to induce protein kinase C activation, which in turn initiates nuclear factor-κB (NF-κB) activation and finally induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release in RAW 264.7 macrophages. In this study, we further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt, and p38 mitogen-activated protein kinase (MAPK) in LTA-induced iNOS expression and NO release in RAW 264.7 macrophages. Tyrosine kinase inhibitors (genistein and tyrphostin AG126), PI3K inhibitors (wortmannin and LY 294002), and a p38 MAPK inhibitor (SB 203580) attenuated LTA-induced iNOS expression and NO release in concentration-dependent manners. Treatment of RAW 264.7 macrophages with LTA caused time-dependent activations of Akt and p38 MAPK. The LTA-induced Akt activation was inhibited by wortmannin, LY 294002, genistein, and tyrphostin AG126. The LTA-induced p38 MAPK activation was inhibited by genistein, tyrphostin AG126, wortmannin, LY 294002, and SB 203580. The LTA-induced formation of an NF-κB-specific DNA-protein complex in the nucleus was inhibited by wortmannin, LY 294002, genistein, tyrphostin AG126, and SB 203580. Treatment of macrophages with LTA caused an increase in κB-luciferase activity, and this effect was inhibited by tyrphostin AG126, wortmannin, LY 294002, the Akt dominant negative mutant (AktDN), and SB 203580. Based on those findings, we suggest that LTA might activate the PI3K/Akt pathway through tyrosine kinase to induce p38 MAPK activation, which in turn initiates NF-κB activation, and ultimately induces iNOS expression and NO release in RAW 264.7 macrophages.

AB - We previously demonstrated that lipoteichoic acid (LTA) might activate phosphatidylcholine-phospholipase C (PC-PLC) and phosphatidylinositol- phospholipase C (PI-PLC) to induce protein kinase C activation, which in turn initiates nuclear factor-κB (NF-κB) activation and finally induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release in RAW 264.7 macrophages. In this study, we further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt, and p38 mitogen-activated protein kinase (MAPK) in LTA-induced iNOS expression and NO release in RAW 264.7 macrophages. Tyrosine kinase inhibitors (genistein and tyrphostin AG126), PI3K inhibitors (wortmannin and LY 294002), and a p38 MAPK inhibitor (SB 203580) attenuated LTA-induced iNOS expression and NO release in concentration-dependent manners. Treatment of RAW 264.7 macrophages with LTA caused time-dependent activations of Akt and p38 MAPK. The LTA-induced Akt activation was inhibited by wortmannin, LY 294002, genistein, and tyrphostin AG126. The LTA-induced p38 MAPK activation was inhibited by genistein, tyrphostin AG126, wortmannin, LY 294002, and SB 203580. The LTA-induced formation of an NF-κB-specific DNA-protein complex in the nucleus was inhibited by wortmannin, LY 294002, genistein, tyrphostin AG126, and SB 203580. Treatment of macrophages with LTA caused an increase in κB-luciferase activity, and this effect was inhibited by tyrphostin AG126, wortmannin, LY 294002, the Akt dominant negative mutant (AktDN), and SB 203580. Based on those findings, we suggest that LTA might activate the PI3K/Akt pathway through tyrosine kinase to induce p38 MAPK activation, which in turn initiates NF-κB activation, and ultimately 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 - p38 MAPK

KW - PI3K

KW - Raw 264.7 macrophages

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