Premium
Activation of TNF‐α transcription utilizes distinct MAP kinase pathways in different macrophage populations
Author(s) -
Means Terry K.,
Pavlovich Ryan P.,
Roca Dominic,
Vermeulen Mary W.,
Fenton Matthew J.
Publication year - 2000
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 - 10.1002/jlb.67.6.885
Subject(s) - biology , tumor necrosis factor alpha , macrophage , microbiology and biotechnology , transcription (linguistics) , transcription factor , kinase , computational biology , genetics , immunology , gene , in vitro , linguistics , philosophy
Stimulation of macrophages by lipopolysaccharide (LPS) leads to the rapid activation of MAP kinases (MAPK) and the subsequent induction of cytokine gene expression. We sought to determine whether LPS‐inducible cytokine genes were differentially regulated in macrophages derived from different tissues. Our studies revealed that PD98059, an inhibitor of the extracellular‐regulated kinase (ERK) pathway, blocked LPS‐induced activation of tumor necrosis factor α (TNF‐α) gene expression in a murine cell line derived from alveolar macrophages but not in a nonpulmonary macrophage cell line. These findings were confirmed using primary murine alveolar and peritoneal macrophages. This suggests that the TNF‐α promoter contains MAPK‐dependent and ‐independent regulatory elements that are used in a cell type‐specific manner. We also found that differences in MAPK‐regulated signaling were not mediated by NF‐κB, LITAF, Egr‐1, CREB, or ATF2/c‐Jun. Together, these studies demonstrate that transcriptional activation of the TNF‐α gene requires the ERK signaling cascade in selected macrophage populations. J. Leukoc. Biol. 67: 885–893; 2000.