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IL‐8‐induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3)
Author(s) -
Henkels Karen M.,
Frondorf Kathleen,
Gonzalez-Mejia M. Elba,
Doseff Andrea L.,
Gomez-Cambronero Julian
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.11.031
Subject(s) - chemotaxis , janus kinase 3 , microbiology and biotechnology , chemistry , tyrosine kinase , janus kinase , janus kinase 2 , mapk/erk pathway , kinase , signal transduction , biology , receptor , interleukin 12 , biochemistry , in vitro , cytotoxic t cell
Janus kinase 3 (JAK3) is a non‐receptor tyrosine kinase vital to the regulation of T‐cells. We report that JAK3 is a mediator of interleukin‐8 (IL‐8) stimulation of a different class of hematopoietic relevant cells: human neutrophils. IL‐8 induced a time‐ and concentration‐dependent activation of JAK3 activity in neutrophils and differentiated HL‐60 leukemic cells. JAK3 was more robustly activated by IL‐8 than other kinases: p70S6K, mTOR, MAPK or PKC. JAK3 silencing severely inhibited IL‐8‐mediated chemotaxis. Thus, IL‐8 stimulates chemotaxis through a mechanism mediated by JAK3. Further, JAK3 activity and chemotaxis were inhibited by the flavonoid apigenin (4′,5,7‐trihydroxyflavone) at ∼5 nM IC 50 . These new findings lay the basis for understanding the molecular mechanism of cell migration as it relates to neutrophil‐mediated chronic inflammatory processes.