Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro

International Immunopharmacology
Sung Chian ChueW S Fred Wong

Abstract

Upon cross-linking of the high-affinity IgE receptors on mast cells, a family of mitogen-activated protein kinases (MAPKs) is activated. The present study examined the effects of p42/44 MAPK kinase inhibitor U0126 and p38 MAPK inhibitors SB220025 and PD169316 on ovalbumin (OVA)-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from lung fragments. Guinea pigs were actively sensitized by OVA. OVA induced anaphylactic bronchial contractions, and release of histamine and peptidoleukotrienes from lung fragments. U0126 (0.3-30 microM), but not SB220025 and PD169316 (3-30 microM), slightly suppressed peak OVA-induced bronchial contraction but markedly reduced anaphylactical contraction over a 50-min period in a dose-dependent manner. U0126 did not inhibit bronchial contractions induced by KCl, histamine or leukotriene D4. U0126 produced a slight reduction in OVA-induced release of histamine but a significant inhibition on the release of peptidoleukotrienes from lung fragments. Exogenous arachidonic acid-induced release of peptidoleukotrienes was not blocked by U0126. SB220025 and PD169316 had no effect on OVA-induced release of histamine and peptidoleukotrienes. Our data ...Continue Reading

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Citations

Jul 19, 2006·Journal of Biomedical Science·Ben-Ching LiaoKee-Ching G Jeng
Apr 29, 2006·Respiratory Research·Frédérique Le BellegoMara S Ludwig
Feb 22, 2011·Chemico-biological Interactions·Umesh C S YadavSatish K Srivastava
Sep 16, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Umesh C S YadavSatish K Srivastava

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