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Extracellular regulatory kinase (ERK1/2) regulates 15‐lipoxygenase Expression in Primary Human Monocytes
Author(s) -
Bhattacharjee Ashish,
Pal Srabani,
Feldman Gerald M,
Cathcart Martha K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.902.5
Subject(s) - microbiology and biotechnology , signal transduction , protein kinase c , kinase , p38 mitogen activated protein kinases , mapk/erk pathway , lipid signaling , inflammation , regulator , biology , chemistry , biochemistry , gene , immunology
Interleukin‐13 (IL‐13) induces the expression of the lipid‐oxidizing enzyme 15‐lipoxygenase (15‐LO) in primary human monocytes. 15‐LO catalyzes the oxygenation of certain polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which play an important role in the pathogenesis of atherosclerosis and inflammation. Previously we identified the functional IL‐13 receptor components, the association of Jaks and the activation of Stats. We have also observed the involvement of a cytosolic signaling complex containing Stat3, p38MAPK and PKCδ, in regulating 15‐LO. Our recent data demonstrate that ERK1/2, another MAP kinase, is involved in regulating IL‐13‐stimulated 15‐LO expression in monocytes. IL‐13 induces the activation of ERK1/2 in a time‐dependent manner. Our results show that the ERK1/2 pharmacological inhibitors block both IL‐13 induction of 15‐LO mRNA as well as protein expression. We further demonstrate that ERK1/2 is present in the signaling complex along with p38MAPK, and PKCδ and that ERK1/2 activity has no role in regulating this complex formation. Further investigations revealed that the PKCδ, p38 MAPK and ERK1/2 pathways are independent, parallel pathways, but are indispensable for 15‐LO expression. Our current studies are focused on exploring the mechanisms by which ERK1/2 regulates the gene expression of 15‐LO, an important regulator of inflammation and apoptosis. (This work was funded by HL51068)