Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinase and protein kinase C

Katsuhiro Zen, Junichi Masuda, Toshiyuki Sasaguri, Chiya Kosaka, Jun Ogata

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The present study investigated the signal transduction pathways leading to the gene expression for monocyte chemoattractant protein-1 (MCP-1) in human monocytes. By Northern blot analysis, MCP-1 mRNA was undetectable in freshly isolated monocytes, but was induced and reached a maximal level at 4 h during culture. The level of accumulated mRNA altered with cell density of the monocytes and was highest at a density of 1 X 106 cells/ml. Nuclear run-on assay demonstrated that this cell density-dependent expression of MCP-1 mRNA was regulated at the transcriptional level, and protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, completely abrogated this gene transcription. Immunoblot analysis for phosphotyrosine in whole cell lysates demonstrated gradual increases in tyrosine phosphorylation of 55-, 60-, and 7O-kDa proteins during culture. Cell density regulated tyrosine phosphorylation of 70-kDa protein in parallel with alterations in MCP-1 mRNA expression. The protein kinase C (PKC) inhibitor H-7 also abrogated the gene transcription and suppressed tyrosine phosphorylation of 70-kDa protein, whereas HA1004, a structural analogue of H-7, did not. These results suggest that MCP-1 gene expression in cultured monocytes is regulated by the cell density at the transcriptional level and that the signaling pathways leading to the gene transcription are mediated through PTK and PKC. It is also suggested that PRC activity plays a critical role in tyrosine phosphorylation of 70-kDa protein, which may mediate signals regulating the cell density-dependent expression of the MCP-1 gene.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalExperimental Cell Research
Volume215
Issue number1
DOIs
Publication statusPublished - Nov 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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