Protein kinase C inhibition enhances platelet-activating factor-induced eicosanoid production in human eosinophils

American Journal of Respiratory Cell and Molecular Biology
G DentK F Rabe

Abstract

Previous investigations have suggested that protein kinase C (PKC) may regulate guinea pig eosinophil responses through a suppressive "negative feedback" mechanism. Using the selective PKC inhibitors bisindolylmaleimide I (Bis I, GF 109203X) and calphostin C, we examined the role of PKC in platelet-activating factor (PAF)-induced respiratory burst and generation of arachidonic acid metabolites in human peripheral blood eosinophils. Bis I inhibited PAF-induced generation of superoxide anion with substantially lower potency (geometric mean IC50 = 1.41 microM, 95% CI 0.94-2.11 microM) than it exhibited against responses to the phorbol esters 4-beta-phorbol 12-myristate 13-acetate (PMA; IC50 = 0.25 microM, 0.09-0.72 microM; P < 0.01) and 4-beta-phorbol 12,13-dibutyrate (IC50 = 0.48 microM, 0.20-1.14 microM; P < 0.05). The production of thromboxane (measured as TxB2) induced by 1 microM PAF was increased significantly by Bis I at concentrations of 1 microM (162 +/- 7.5% of control PAF response; P < 0.01) and 10 microM (194 +/- 17%; P < 0.001); TxB2 release induced by PMA was unaffected by concentrations of Bis I up to 1 microM and inhibited by 10 microM Bis I (48 +/- 11%; P < 0.05). Bis I (1 microM) significantly increased both thro...Continue Reading

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Citations

Dec 19, 2001·Journal of Cellular Physiology·J L Bankers-FulbrightS M O'Grady
Jan 5, 2000·European Journal of Pharmacology·G P SamokhinR A Henriksen
Feb 15, 2000·American Journal of Respiratory and Critical Care Medicine·D Schmidt, K F Rabe
Mar 6, 2004·American Journal of Respiratory and Critical Care Medicine·Gordon DentRatko Djukanovic
Nov 1, 2006·Allergology International : Official Journal of the Japanese Society of Allergology·Takafumi YamaguchiMasahiko Kato
Sep 26, 2000·Pulmonary Pharmacology & Therapeutics·M A GiembyczM A Lindsay
Mar 25, 2006·International Archives of Allergy and Immunology·G Sandra TjabringaPieter S Hiemstra
May 3, 2000·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·T OshiroK Shirato
Aug 9, 2018·Scientific Reports·Carlos Fernando Odir Rodrigues MeloRodrigo Ramos Catharino
Aug 10, 2002·The Journal of Allergy and Clinical Immunology·Takumi TakizawaAkihiro Morikawa
Apr 22, 2003·The Journal of Allergy and Clinical Immunology·Satoshi Miike, Hirohito Kita

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