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Autocrine regulation of collagenase gene expression by TNF‐α in U937 cells
Author(s) -
Callaghan Máire M.,
Lovis Rosa M.,
Rammohan Chidambaram,
Lu Yang,
Pope Richard M.
Publication year - 1996
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.59.1.125
Subject(s) - autocrine signalling , microbiology and biotechnology , biology , collagenase , pyrrolidine dithiocarbamate , gene expression , interstitial collagenase , protein kinase c , tumor necrosis factor alpha , cell culture , signal transduction , endocrinology , biochemistry , gene , nf κb , enzyme , genetics
Tumor necrosis factor α (TNF‐α) has been shown to induce the production of interstitial collagenase by fibroblasts and chondrocytes. We investigated the role of TNF‐α in collagenase gene expression by U937 monocyte/macrophage cells. Transcription of the TNF‐α gene was observed after 0.5 h of phorbol myristate acetate (PMA) stimulation. Collagenase mRNA expression was not observed until 5–7 h of activation with PMA. TNF‐α was detected in the culture supernatants 2–3 h before transcription of the collagenase gene. Neutralization of TNF‐α protein with anti‐TNF‐α antibodies significantly reduced collagenase mRNA expression. Protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibition essentially abolished both PMA‐induced TNF‐α protein secretion and collagenase mRNA expression. Collagenase gene expression induced by exogenous TNF‐α in U937 cells stimulated with a suboptimal concentration of PMA was sup‐pressed by PTK, but not PKC, inhibition. The pyrrolidine derivative of dithiocarbamate, a potent inhibitor of nuclear factor‐κB (NF‐κB) activation, resulted in a marked reduction in collagenase gene transcription, however, no reduction of TNF‐α secretion was noted. Anti‐TNF‐α antibodies inhibited PMA‐induced NF‐κB activation. These observations demonstrate an important role for TNF‐α in the autocrine regulation of collagenase gene expression by U937 cells. Additionally, TNF‐α‐induced PTK and NF‐κB activation were important in collagenase gene expression in this cell line.