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Biomedical subjects

A Uthman

Publications and source records attributed to A Uthman.

7 recordsLinked to original sources

Regulation of interleukin-8 gene expression by all-trans retinoic acid.

We have studied the relationship between interleukin-8 (IL-8) and interleukin-1 alpha (IL-1 alpha) release after stimulation with all-trans retinoic acid (ATRA) and tumor necrosis factor-alpha (TNF-alpha) in the human epithelial ovarian cancer cell line HOC-7. Both IL-1 alpha and IL-8 protein release were enhanced by treatment with ATRA and TNF-alpha after 48 h exposure. Blocking of IL-1 alpha activity in HOC-7 cells with either IL-1 receptor antagonist (IL-1ra) or a neutralizing antibody directed against IL-1 alpha resulted in a dose-dependent decrease of IL-8 release by ATRA, TNF-alpha and IL-1 alpha treated HOC-7 cells. Expression of IL-8 mRNA was enhanced by the individual stimuli, whereas co-treatment with IL-1ra resulted in a loss of IL-8 specific transcripts, except in TNF-alpha treated cells. Inhibition of de novo protein synthesis by cycloheximide (CHX) and simultaneous blocking of IL-1 alpha activity by IL-1ra for 24 h revealed that ATRA controls IL-8 gene expression transcriptionally and that the extent of IL-8 protein release can be markedly influenced by cellular expressed IL-1 alpha.

Adenocarcinoma

Human keratinocytes express the three major splice forms of vascular endothelial growth factor.

Vascular endothelial growth factor is a powerful mitogen for endothelial cells, recently reported to be produced by keratinocytes. In the present work, we examined human keratinocytes in primary culture for the splice variants of vascular endothelial growth factor. In situ hybridization revealed that 100% of cultured human keratinocytes expressed mRNA for this cytokine, and analysis by reverse transcriptase-polymerase chain reaction indicated that three species of mRNA were produced. Southern hybridization and size calculations of PCR products revealed mRNA species corresponding to 121, 165, and 189 amino-acid forms of this cytokine. Using a rabbit anti-vascular endothelial growth factor antiserum, we radioimmunoprecipitated two molecular weight forms (approximately 45 and 58 kDa, non-reducing conditions) from keratinocyte culture supernatants. Under reducing conditions, three bands of approximately 15, 20, and 24 kDa appeared, corresponding with the predominant forms of vascular endothelial growth factor described. We propose that secretion of vascular endothelial growth factor by human keratinocytes in vivo sustains angiogenesis during physiologic tissue repair and in pathologic states accompanied by neovascularization.

Cells, Cultured