Tags

Type your tag names separated by a space and hit enter

Activation and induction of cytosolic phospholipase A2 by TNF-α mediated through Nox2, MAPKs, NF-κB, and p300 in human tracheal smooth muscle cells.
J Cell Physiol. 2011 Aug; 226(8):2103-14.JC

Abstract

Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-α (TNF-α). However, the mechanisms underlying TNF-α-induced cPLA(2) expression and PGE(2) synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we report that TNF-α-induced cPLA(2) protein and mRNA expression, PGE(2) production, and phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, which were attenuated by pretreatment with a ROS scavenger [N-acetyl-L-cysteine, (NAC)] and the inhibitors of NADPH oxidase [apocynin (APO) and diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNA of Nox2, p47(phox) , MEK1, p42, p38, or JNK2. TNF-α-induced cPLA(2) expression was also inhibited by pretreatment with a selective NF-κB inhibitor [helenalin (HLN)] or transfection with dominant negative mutants of NF-κB inducing kinase (NIK) or IκB kinase (IKK)α/β. TNF-α-induced NF-κB translocation was blocked by pretreatment with NAC, DPI, APO, or HLN, but not by U0126, SB202190, or SP600125. In addition, pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA blocked cPLA(2) expression and PGE(2) synthesis induced by TNF-α. We further confirmed that p300 was associated with the cPLA(2) promoter which was dynamically linked to histone H4 acetylation stimulated by TNF-α, determined by chromatin immunoprecipitation assay. Association of p300 and histone H4 to cPLA(2) promoter was inhibited by U0126, SB202190, and SP600125. These results suggested that in HTSMCs, activation of p47(phox) , MAPKs, NF-κB, and p300 is essential for TNF-α-induced cPLA(2) expression and PGE(2) release.

Authors+Show Affiliations

Department of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology, Chia-Yi, Taiwan.No 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

21520062

Citation

Lee, Chiang-Wen, et al. "Activation and Induction of Cytosolic Phospholipase A2 By TNF-α Mediated Through Nox2, MAPKs, NF-κB, and P300 in Human Tracheal Smooth Muscle Cells." Journal of Cellular Physiology, vol. 226, no. 8, 2011, pp. 2103-14.
Lee CW, Lin CC, Lee IT, et al. Activation and induction of cytosolic phospholipase A2 by TNF-α mediated through Nox2, MAPKs, NF-κB, and p300 in human tracheal smooth muscle cells. J Cell Physiol. 2011;226(8):2103-14.
Lee, C. W., Lin, C. C., Lee, I. T., Lee, H. C., & Yang, C. M. (2011). Activation and induction of cytosolic phospholipase A2 by TNF-α mediated through Nox2, MAPKs, NF-κB, and p300 in human tracheal smooth muscle cells. Journal of Cellular Physiology, 226(8), 2103-14. https://doi.org/10.1002/jcp.22537
Lee CW, et al. Activation and Induction of Cytosolic Phospholipase A2 By TNF-α Mediated Through Nox2, MAPKs, NF-κB, and P300 in Human Tracheal Smooth Muscle Cells. J Cell Physiol. 2011;226(8):2103-14. PubMed PMID: 21520062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation and induction of cytosolic phospholipase A2 by TNF-α mediated through Nox2, MAPKs, NF-κB, and p300 in human tracheal smooth muscle cells. AU - Lee,Chiang-Wen, AU - Lin,Chih-Chung, AU - Lee,I-Ta, AU - Lee,Hui-Chun, AU - Yang,Chuen-Mao, PY - 2011/4/27/entrez PY - 2011/4/27/pubmed PY - 2011/7/27/medline SP - 2103 EP - 14 JF - Journal of cellular physiology JO - J Cell Physiol VL - 226 IS - 8 N2 - Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-α (TNF-α). However, the mechanisms underlying TNF-α-induced cPLA(2) expression and PGE(2) synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we report that TNF-α-induced cPLA(2) protein and mRNA expression, PGE(2) production, and phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, which were attenuated by pretreatment with a ROS scavenger [N-acetyl-L-cysteine, (NAC)] and the inhibitors of NADPH oxidase [apocynin (APO) and diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNA of Nox2, p47(phox) , MEK1, p42, p38, or JNK2. TNF-α-induced cPLA(2) expression was also inhibited by pretreatment with a selective NF-κB inhibitor [helenalin (HLN)] or transfection with dominant negative mutants of NF-κB inducing kinase (NIK) or IκB kinase (IKK)α/β. TNF-α-induced NF-κB translocation was blocked by pretreatment with NAC, DPI, APO, or HLN, but not by U0126, SB202190, or SP600125. In addition, pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA blocked cPLA(2) expression and PGE(2) synthesis induced by TNF-α. We further confirmed that p300 was associated with the cPLA(2) promoter which was dynamically linked to histone H4 acetylation stimulated by TNF-α, determined by chromatin immunoprecipitation assay. Association of p300 and histone H4 to cPLA(2) promoter was inhibited by U0126, SB202190, and SP600125. These results suggested that in HTSMCs, activation of p47(phox) , MAPKs, NF-κB, and p300 is essential for TNF-α-induced cPLA(2) expression and PGE(2) release. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/21520062/Activation_and_induction_of_cytosolic_phospholipase_A2_by_TNF_α_mediated_through_Nox2_MAPKs_NF_κB_and_p300_in_human_tracheal_smooth_muscle_cells_ L2 - https://doi.org/10.1002/jcp.22537 DB - PRIME DP - Unbound Medicine ER -