Pharmacological Effects of SB 220025, a Selective Inhibitor of P38 Mitogen-Activated Protein Kinase, in Angiogenesis and Chronic Inflammatory Disease Models

摘要: Chronic inflammatory diseases often are accompanied by intense angiogenesis, supporting the destructive proliferation of tissues. A model angiogenesis is murine air pouch granuloma, which has a hyperangiogenic component. In this model, we explored regulation using SB 220025, specific inhibitor human p38 mitogen-activated protein (MAP) kinase, with an IC50 value 60 nM and 50- to 1000-fold selectivity vs. other kinases tested. vivo , compound reduced lipopolysaccharide-induced production tumor necrosis factor at ED50 7.5 mg/kg. over course granuloma development, observed elevated levels interleukin-1β factor-α during chronic phase when occurs. 220025 30 mg/kg b.i.d. p.o. was able greatly reduce expression these cytokines inhibit ≈40%. To further study effects p38/CSBP MAP kinase inhibition in angiogenesis-dependent disease, tested collagen-induced arthritis. prevent progression established Thus, inhibitor, can cytokine effective treatment for proliferative disease.