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.
Harant
H
H
Department of Internal Medicine I, University Hospital of Vienna, Austria.
Lindley
I
I
Uthman
A
A
Ballaun
C
C
Krupitza
G
G
Grunt
T
T
Huber
H
H
Dittrich
C
C
D000230:Adenocarcinoma; D015152:Blotting, Northern; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D010051:Ovarian Neoplasms; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin