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Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A, p38 MAPK, and nuclear factor-kappaB pathways.
Cell Signal 2006; 18(8):1235-43CS

Abstract

We recently reported that lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus, stimulated inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) release, and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. This study was carried out to further investigate the roles of COX-2 and prostaglandin E2 (PGE2) in LTA-induced iNOS expression and NO release in RAW 264.7 macrophages. Treatment of RAW 264.7 macrophages with LTA caused a time-dependent increase in PGE2 release. LTA-induced iNOS expression and NO release were inhibited by a non-selective COX inhibitor (indomethacin), a selective COX-2 inhibitor (NS-398), an adenylyl cyclase (AC) inhibitor (dideoxyadenosine, DDA), and a protein kinase A (PKA) inhibitor (KT-5720). Furthermore, both PGE2 and the direct PKA activator, dibutyryl-cAMP, also induced iNOS expression in a concentration-dependent manner. Stimulation of RAW 264.7 macrophages with LTA, PGE2, and dibutyryl-cAMP all caused p38 MAPK activation in a time-dependent manner. LTA-mediated p38 MAPK activation was inhibited by indomethacin, NS-398, and SB 203580, but not by PD 98059. The PGE2-mediated p38 MAPK activation was inhibited by DDA, KT-5720, and SB 203580, but not by PD 98059. LTA caused time-dependent activation of the nuclear factor-kappaB (NF-kappaB)-specific DNA-protein complex formation. The LTA-induced increase in kappaB-luciferase activity was inhibited by indomethacin, NS-398, KT-5720, and a dominant negative mutant of p38 alphaMAPK (p38 alphaMAPK DN). These results suggest that LTA-induced iNOS expression and NO release involve COX-2-generated PGE2 production, and AC, PKA, p38 MAPK, and NF-kappaB activation in RAW 264.7 macrophages.

Authors+Show Affiliations

Department of Cardiac Surgery, Taipei Medical University, Wang Fang Hospital, Taipei, Taiwan; Graduate Institute of Injury Prevention, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16289764

Citation

Chang, Yau-Chong, et al. "Lipoteichoic Acid-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages Is Mediated By Cyclooxygenase-2, Prostaglandin E2, Protein Kinase A, P38 MAPK, and Nuclear factor-kappaB Pathways." Cellular Signalling, vol. 18, no. 8, 2006, pp. 1235-43.
Chang YC, Li PC, Chen BC, et al. Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A, p38 MAPK, and nuclear factor-kappaB pathways. Cell Signal. 2006;18(8):1235-43.
Chang, Y. C., Li, P. C., Chen, B. C., Chang, M. S., Wang, J. L., Chiu, W. T., & Lin, C. H. (2006). Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A, p38 MAPK, and nuclear factor-kappaB pathways. Cellular Signalling, 18(8), pp. 1235-43.
Chang YC, et al. Lipoteichoic Acid-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages Is Mediated By Cyclooxygenase-2, Prostaglandin E2, Protein Kinase A, P38 MAPK, and Nuclear factor-kappaB Pathways. Cell Signal. 2006;18(8):1235-43. PubMed PMID: 16289764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A, p38 MAPK, and nuclear factor-kappaB pathways. AU - Chang,Yau-Chong, AU - Li,Pei-Chih, AU - Chen,Bing-Chang, AU - Chang,Ming-Shyan, AU - Wang,Jui-Ling, AU - Chiu,Wen-Ta, AU - Lin,Chien-Huang, Y1 - 2005/11/11/ PY - 2005/09/07/received PY - 2005/10/03/accepted PY - 2005/11/18/pubmed PY - 2006/7/27/medline PY - 2005/11/18/entrez SP - 1235 EP - 43 JF - Cellular signalling JO - Cell. Signal. VL - 18 IS - 8 N2 - We recently reported that lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus, stimulated inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) release, and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. This study was carried out to further investigate the roles of COX-2 and prostaglandin E2 (PGE2) in LTA-induced iNOS expression and NO release in RAW 264.7 macrophages. Treatment of RAW 264.7 macrophages with LTA caused a time-dependent increase in PGE2 release. LTA-induced iNOS expression and NO release were inhibited by a non-selective COX inhibitor (indomethacin), a selective COX-2 inhibitor (NS-398), an adenylyl cyclase (AC) inhibitor (dideoxyadenosine, DDA), and a protein kinase A (PKA) inhibitor (KT-5720). Furthermore, both PGE2 and the direct PKA activator, dibutyryl-cAMP, also induced iNOS expression in a concentration-dependent manner. Stimulation of RAW 264.7 macrophages with LTA, PGE2, and dibutyryl-cAMP all caused p38 MAPK activation in a time-dependent manner. LTA-mediated p38 MAPK activation was inhibited by indomethacin, NS-398, and SB 203580, but not by PD 98059. The PGE2-mediated p38 MAPK activation was inhibited by DDA, KT-5720, and SB 203580, but not by PD 98059. LTA caused time-dependent activation of the nuclear factor-kappaB (NF-kappaB)-specific DNA-protein complex formation. The LTA-induced increase in kappaB-luciferase activity was inhibited by indomethacin, NS-398, KT-5720, and a dominant negative mutant of p38 alphaMAPK (p38 alphaMAPK DN). These results suggest that LTA-induced iNOS expression and NO release involve COX-2-generated PGE2 production, and AC, PKA, p38 MAPK, and NF-kappaB activation in RAW 264.7 macrophages. SN - 0898-6568 UR - https://www.unboundmedicine.com/medline/citation/16289764/Lipoteichoic_acid_induced_nitric_oxide_synthase_expression_in_RAW_264_7_macrophages_is_mediated_by_cyclooxygenase_2_prostaglandin_E2_protein_kinase_A_p38_MAPK_and_nuclear_factor_kappaB_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(05)00266-4 DB - PRIME DP - Unbound Medicine ER -