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p38 MAP kinase mediates stress‐induced leukotriene synthesis in a human B‐lymphocyte cell line
Author(s) -
Werz Oliver,
Klemm Jenny,
Rådmark Olof,
Samuelsson Bengt
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.70.5.830
Subject(s) - mitogen activated protein kinase , p38 mitogen activated protein kinases , biology , kinase , protein kinase a , microbiology and biotechnology , mapk14 , biochemistry , mitogen activated protein kinase kinase
5‐Lipoxygenase (5‐LO), which catalyzes the first two steps in leukotriene biosynthesis, is a target for pharmacological treatment of inflammatory disorders. Previous studies have shown that B‐lymphocytes express 5‐LO. Here we demonstrate that several stimuli of cell stress such as osmotic shock (sorbitol, NaCl), oxidative stress (hydrogen peroxide, diamide), chemical stress sodium arsenite, and inflammatory cytokines enhanced cellular 5‐LO activity in a B cell line (BL41‐E95‐A), when added simultaneously with ionophore plus arachidonate. It is interesting that sorbitol alone was sufficient for 5‐LO product formation in the presence of exogenous arachidonic acid. These stimuli also activated p38 mitogen‐activated protein (MAP) kinase and downstream MAP kinase‐activated protein kinases in BL41‐E95‐A cells, which could phosphorylate 5‐LO or heat shock protein 27 in vitro. The p38 MAP kinase inhibitor SB203580 abolished stress‐induced leukotriene synthesis in B cells, without inhibition of 5‐LO catalytic activity in cell‐free systems. Our results indicate that p38 MAP kinase activation by cell stress is required for efficient leukotriene synthesis in B‐lymphocytes.