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Possible roles of protein kinases in neutrophil chemotactic factor production by leucocytes in allergic inflammation in rats
Author(s) -
Tanabe JunIchi,
Watanabe Masako,
Kondoh Sachiko,
Mue Suetsugu,
Ohuchi Kazuo
Publication year - 1994
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.1476-5381.1994.tb17163.x
Subject(s) - chemotaxis , protein kinase a , genistein , kinase , tyrosine kinase , protein kinase inhibitor , microbiology and biotechnology , chemistry , biology , biochemistry , endocrinology , signal transduction , receptor
1 In an air pouch‐type allergic inflammation model in rats, leucocytes that had infiltrated into the pouch fluid collected 4 h after the antigen challenge produced proteinaceous chemotactic factors for neutrophils when they were incubated in the medium. 2 To clarify the mechanism of activation of the infiltrated leucocytes in producing these factors, the effects of protein kinase inhibitors on neutrophil chemotactic factor production were examined. 3 When the infiltrated leucocytes were incubated for 4h in medium containing the non‐selective protein kinase inhibitor K‐252a (1–100 ng ml −1 , 2.14–214 n m ), the tyrosine kinase inhibitor genistein (1–50 μg ml −1 , 3.7–185 μ m ), and the more selective protein kinase C inhibitor H‐7 (5–100 μg ml −1 , 13.7–274 μ m ); neutrophil chemotactic activity in the conditioned medium was decreased in a concentration‐dependent manner, but the adenosine 3′:5′‐cyclic monophosphate (cAMP)‐dependent protein kinase inhibitor H‐89 (1–1000 ng ml −1 , 2.24–2240 n m ) showed no effect. 4 Isoelectric focusing of the conditioned medium revealed that the leucocytes produced two neutrophil chemotactic factors, leucocyte‐derived neutrophil chemotactic factor (LDNCF) 1 and LDNCF‐2. Treatment of the leucocytes with K‐252a, genistein, and H‐7, but not H‐89, inhibited production of both LDNCF‐1 and LDNCF‐2. 5 These results suggest that activation of tyrosine kinase and protein kinase C., but not cAMP‐dependent protein kinase, is responsible for the production of LDNCF‐1 and LDNCF‐2. 6 The steroidal anti‐inflammatory drug dexamethasone and the protein synthesis inhibitor cyclohex‐imide inhibited neutrophil chemotactic factor production in a concentration‐dependent manner. Time‐course experiments showed that the inhibitory effect by dexamethasone was apparent even 30min after the incubation. 7 Mechanism for inhibiting the production of LDNCF‐1 and LDNCF‐2 by dexamethasone is also discussed.