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Stimulation of protein kinase C redistribution and inhibition of leukotriene B 4 ‐induced inositol 1,4,5‐trisphosphate generation in human neutrophils by lipoxin A 4
Author(s) -
Chungaon Keith O.,
Soyombo Olukayode,
Spur Bernd W.,
Lee Tak H.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16733.x
Subject(s) - protein kinase c , inositol , leukotriene b4 , second messenger system , stimulation , lipid signaling , phosphorylation , microbiology and biotechnology , biology , chemistry , receptor , endocrinology , biochemistry , immunology , inflammation
1 To test the hypothesis that protein kinase C (PKC) is involved in the inhibitory actions of lipoxin A 4 (LXA 4 ) on second messenger generation, we studied the effects of LXA 4 on PKC in human neutrophils and on leukotriene B 4 (LTB 4 )‐stimulated inositol‐1,4,5‐trisphosphate (Ins(1,4,5)P 3 ) generation. 2 LXA 4 , 1 μ m , caused a fall in cytosolic PKC‐dependent histone phosphorylating activity to 23.5% of basal levels. 3 LXA 4 , caused an increase in particulate PKC‐dependent histone phosphorylating activity with a bell‐shaped dose‐response fashion; maximal stimulation was observed at 10 nM LXA 4 . 4 Western blot analysis with affinity‐purified antibodies to α‐ and β‐PKC showed that only the β‐PKC isotype was translocated by LXA 4 . 5 LXA 4 inhibited LTB 4 ‐stimulated Ins(1,4,5)P 3 generation in a bell‐shaped fashion with maximal inhibition at 1 nM LXA 4 . The observed inhibition was dose‐dependently removed by pre‐incubation with a PKC inhibitor (Ro‐31–8220). 6 These results show that LXA 4 activates PKC in whole cells and supports a role for PKC activation in the inhibitory action of LXA 4 on LTB 4 ‐induced Ins(1,4,5)P 3 generation. 7 LXA 4 (1 − 1000 nM) pre‐incubation did not affect specific binding of [ 3 H]‐LTB 4 to neutrophils. Thus, the inhibitory effect of LXA 4 on LTB 4 ‐stimulated Ins(1,4,5)P 3 generation could not be attributed to an effect on LTB 4 receptors.