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Src family protein tyrosine kinase signaling mediates monosodium urate crystal‐induced IL‐8 expression by monocytic THP‐1 cells
Author(s) -
Liu Ru,
Aupperle Karl,
Terkeltaub Robert
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.6.961
Subject(s) - tyrosine protein kinase csk , lyn , proto oncogene tyrosine protein kinase src , kinase , biology , tyrosine kinase , microbiology and biotechnology , src family kinase , phosphorylation , signal transduction , sh3 domain
Neutrophil‐dependent inflammation dependent on monosodium urate (MSU)crystal‐induced IL‐8 expression occurs in gout. MSU crystals activatephagocyte Src family tyrosine kinases and the serine/threonine kinasep70s6k. Thus, using monocytic THP‐1 cells, we assessed the potentialfor Src family kinases and p70s6k to mediate MSU‐induced IL‐8expression. MSU crystals induced phosphorylation of p70s6k and the Srckinases c‐Src, Lyn, Hck, and Fyn. IL‐8 expression was attenuated moreby the Src kinase inhibitor PP1 than by the p70s6k inhibitor rapamycin.PP1 inhibited crystal‐induced phosphorylation of ERK1/2 and IκBαand suppressed IκB kinase (IKK) activation and NF‐κB binding to theIL‐8 promoter, signals that mediate MSU‐induced IL‐8 expression.Transfection of the native Src inhibitor, C‐terminal Src kinase (Csk),also suppressed crystal‐induced c‐Src, ERK1/2, and IκBαphosphorylation and IL‐8 expression. We conclude that Src familytyrosine kinase signaling plays a significant role in MSUcrystal‐induced IL‐8 expression via stimulation of ERK1/2 pathway andNF‐κB activation.