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Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells.
Toxicol Appl Pharmacol. 2008 Nov 01; 232(3):396-407.TA

Abstract

Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid release for prostaglandin (PG) synthesis during stimulation with interleukin-1beta (IL-1beta). However, the mechanisms underlying IL-1beta-induced cPLA2 expression and PGE2 synthesis by canine tracheal smooth muscle cells (CTSMCs) have not been defined. IL-1beta induced cPLA2 protein and mRNA expression, PGE2 production, and phosphorylation of p42/p44 MAPK, p38 MAPK (ATF2), and JNK (c-Jun) in a time- and concentration-dependent manner, determined by Western blotting, RT-PCR, and ELISA, which was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), or transfection with dominant negative mutants of MEK1/2, p38, and JNK, respectively. Furthermore, IL-1beta-induced cPLA2 expression and PGE2 synthesis was inhibited by a selective NF-kappaB inhibitor (helenalin) or transfection with dominant negative mutants of NF-kappaB inducing kinase (NIK), IkappaB kinase (IKK)-alpha, and IKK-beta. Consistently, IL-1beta stimulated both IkappaB-alpha degradation and NF-kappaB translocation into nucleus in these cells. NF-kappaB translocation was blocked by helenalin, but not by U0126, SB202190, and SP600125. MAPKs together with NF-kappaB-activated p300 recruited to cPLA2 promoter thus facilitating the binding of NF-kappaB to cPLA2 promoter region and expression of cPLA2 mRNA. IL-1beta-induced cPLA2 expression and PGE2 production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses. These results suggest that in CTSMCs, IL-1beta-induced cPLA2 expression and PGE2 synthesis was independently mediated through activation of MAPKs and NF-kappaB pathways and was connected to p300 recruitment and activation.

Authors+Show Affiliations

Department of Internal Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.No affiliation info availableNo 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

18708082

Citation

Luo, Shue-Fen, et al. "Involvement of MAPKs, NF-kappaB and P300 Co-activator in IL-1beta-induced Cytosolic Phospholipase A2 Expression in Canine Tracheal Smooth Muscle Cells." Toxicology and Applied Pharmacology, vol. 232, no. 3, 2008, pp. 396-407.
Luo SF, Lin CC, Chen HC, et al. Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells. Toxicol Appl Pharmacol. 2008;232(3):396-407.
Luo, S. F., Lin, C. C., Chen, H. C., Lin, W. N., Lee, I. T., Lee, C. W., Hsiao, L. D., & Yang, C. M. (2008). Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells. Toxicology and Applied Pharmacology, 232(3), 396-407. https://doi.org/10.1016/j.taap.2008.07.019
Luo SF, et al. Involvement of MAPKs, NF-kappaB and P300 Co-activator in IL-1beta-induced Cytosolic Phospholipase A2 Expression in Canine Tracheal Smooth Muscle Cells. Toxicol Appl Pharmacol. 2008 Nov 1;232(3):396-407. PubMed PMID: 18708082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells. AU - Luo,Shue-Fen, AU - Lin,Chih-Chung, AU - Chen,Hsin-Chieh, AU - Lin,Wei-Ning, AU - Lee,I-Ta, AU - Lee,Chiang-Wen, AU - Hsiao,Li-Der, AU - Yang,Chuen-Mao, Y1 - 2008/07/29/ PY - 2008/03/11/received PY - 2008/07/01/revised PY - 2008/07/17/accepted PY - 2008/8/19/pubmed PY - 2008/11/7/medline PY - 2008/8/19/entrez SP - 396 EP - 407 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 232 IS - 3 N2 - Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid release for prostaglandin (PG) synthesis during stimulation with interleukin-1beta (IL-1beta). However, the mechanisms underlying IL-1beta-induced cPLA2 expression and PGE2 synthesis by canine tracheal smooth muscle cells (CTSMCs) have not been defined. IL-1beta induced cPLA2 protein and mRNA expression, PGE2 production, and phosphorylation of p42/p44 MAPK, p38 MAPK (ATF2), and JNK (c-Jun) in a time- and concentration-dependent manner, determined by Western blotting, RT-PCR, and ELISA, which was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), or transfection with dominant negative mutants of MEK1/2, p38, and JNK, respectively. Furthermore, IL-1beta-induced cPLA2 expression and PGE2 synthesis was inhibited by a selective NF-kappaB inhibitor (helenalin) or transfection with dominant negative mutants of NF-kappaB inducing kinase (NIK), IkappaB kinase (IKK)-alpha, and IKK-beta. Consistently, IL-1beta stimulated both IkappaB-alpha degradation and NF-kappaB translocation into nucleus in these cells. NF-kappaB translocation was blocked by helenalin, but not by U0126, SB202190, and SP600125. MAPKs together with NF-kappaB-activated p300 recruited to cPLA2 promoter thus facilitating the binding of NF-kappaB to cPLA2 promoter region and expression of cPLA2 mRNA. IL-1beta-induced cPLA2 expression and PGE2 production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses. These results suggest that in CTSMCs, IL-1beta-induced cPLA2 expression and PGE2 synthesis was independently mediated through activation of MAPKs and NF-kappaB pathways and was connected to p300 recruitment and activation. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/18708082/Involvement_of_MAPKs_NF_kappaB_and_p300_co_activator_in_IL_1beta_induced_cytosolic_phospholipase_A2_expression_in_canine_tracheal_smooth_muscle_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(08)00319-0 DB - PRIME DP - Unbound Medicine ER -