Abstract
The early growth response-1 (Egr-1) gene has been identified as a nuclear transcriptional factor and implicated in the regulation of growth and differentiation of osteoblastic cells. In the present study, we investigated whether Egr-1 mRNA is expressed and induced by interleukin-1 beta, (IL-beta) and tumor necrosis factor-alpha (TNF-alpha) in normal human bone marrow stromal (HBMS) and osteoblastic (HOB) cells. Results demonstrate a very low basal expression of Egr-I mRNA which is induced by IL-1 beta, and TNF-alpha in a time- and dose-dependent manner. Egr-1 mRNA induction was detectable within 15 min, reached maximal by 60 min and thereafter declined to basal levels by 120 min. Induction of Egr-1 mRNA by IL-1 beta and TNF-alpha was completely inhibited by H-7 suggesting the mediation of protein kinase C. The induction by IL-1 beta and TNF-alpha of Egr-1 mRNA was independent of de novo protein synthesis since this induction was also observed in the presence of protein synthesis inhibitor cycloheximide. Fetal bovine serum and cycloheximide also independently induced the Egr-1 mRNA. Actinomycin D experiments demonstrated that Egr-1 mRNA is degraded very rapidly with a half-life of 30 min. Our results demonstrate the expression of Egr-1 gene and its induction by IL-1 beta, and TNF-alpha in normal human bone marrow stromal (osteoprogenitor) and osteoblastic cells in primary cultures. Data also reveal that the expression of Egr-1 gene is inhibited by protein kinase C inhibitor H-7 suggesting that the activation of protein kinase C or other protein kinases resulting in the phosphorylation of specific transcription factor(s) is the first immediate early step in the induction of immediate-early Egr-1 gene by IL-1 beta, and TNF-alpha. Results also suggest that Egr-1 is an important mediator of IL-1 beta and TNF-alpha action in normal human osteoblastic cells.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
