Role of P38 MAPK, AP-1, and NF-κB in interleukin-1β-induced IL-8 expression in human vascular smooth muscle cells

摘要: Abstract Interleukin (IL)-1 modulates the expression of various genes in normal and tumor cells. We investigated molecular mechanisms underlying IL-1β-induced IL-8 mRNA protein human vascular smooth muscle cells (hVSMCs). P38 mitogen-activated kinase (MAPK) was activated after 5 min IL-1β treatment, whereas extracellular signal-regulated kinases, c-jun amino-terminal B/Akt were not by IL-1β. induced activation a full-length promoter–reporter construct. Deletional mutagenesis localized IL-1β-responsive domains to two regions (−133 −98 −85 −50) that contain consensus binding sites for activator protein-1 (AP-1) nuclear factor-κB (NF-κB), respectively. Site-directed 133-bp minimal promoter confirmed these required activity. Electrophoretic mobility shift assays increased AP-1 NF-κB DNA-binding activities time-dependent manner. SB203580, specific MAPK inhibitor, partially blocked induction mRNA, activity, extract but DNA binding. Our data demonstrate are essential transcription factors gene hVSMCs. is involved inducing via