Involvement of MAPKs and NF‐κB in cPLA 2 induced by IL‐1β in tracheal smooth muscle cells

Abstract

cPLA2 plays a pivotal role in mediating agonist-induced AA release for PG synthesis during stimulation with IL-1β. However, the signaling pathways mediating cPLA2 expression and PGE2 synthesis by canine tracheal smooth muscle cells (TSMCs) remain unknown. IL-1β-induced cPLA2 expression and PGE2 release were attenuated by inhibitors of tyrosine kinase (genistein), PC-PLC (D609), PI-PLC (U73122), PKC (GF109203X and staurosporine), Ca2+ (BAPTA+EDTA), MEK1/2 (PD98059), p38 (SB202190), JNK (SP600125), and PI3-K (LY294002 and wortmannin). In addition, IL-1β-induced cPLA2 expression and PGE2 synthesis was attenuated by transfection with dominant negative mutants of NF-κB inducing kinase (NIK) and IκB kinase (IKK)-α, but not by IKK-β. Taken together, these findings suggest that the increased expression of cPLA2 correlates with the release of PGE2 from IL-1β-challenged TSMCs, at least in part, mediated through MAPKs and NF-κB signaling pathways. IL-1β-mediated responses were modulated by PLC, Ca2+, PKC, tyrosine kinase, and PI3-K in these cells.