Effects of retinoic acid on interleukin-1 alpha and -1 beta expression by normal human keratinocytes cultured in defined medium.
In human epidermis, basal keratinocytes are the main source of interleukin-1 (IL-1), and IL-1 alpha is the predominant form, whereas IL-1 beta appears to exist predominantly in cultured keratinocytes. We investigated the effects of retinoic acid (RA) treatments on IL-1 alpha and -beta protein and mRNA expression of normal human keratinocytes cultured in low-calcium defined medium with or without hydrocortisone. Radioimmunoassay showed that after stimulation by RA, the IL-1 beta intracellular level is predominantly increased, with no significant modification of IL-1 alpha expression. The addition of hydrocortisone in the culture medium resulted in a decrease in RA-induced IL-1 beta overexpression, without notable modifications in untreated cultures. Release of both IL-1 alpha and -beta in culture supernatants was detectable only after RA treatment and in the absence of hydrocortisone. The overexpression of IL-1 beta in control and RA-treated cultures mainly concerned the 52- and 31- to 36-kD biologically inactive precursor forms. Northern blot using specific IL-1 alpha and -beta oligonucleotide probes showed that IL-1 beta mRNA predominate over IL-1 alpha mRNA and reach a maximal level 6 h before the IL-1 beta protein peak. These findings indicate that in cultured keratinocytes intracellular IL-1 beta is preferentially increased by RA but in its immature forms. The significance of this overexpression remains to be elucidated.
Gatto
H
H
INSERM U 346, affiliée CNRS, Pavillon R, Hôpital E.-Herriot, Lyon, France.
Richard
M H
MH
Viac
J
J
Charveron
M
M
Schmitt
D
D
D000328:Adult; D002118:Calcium / Q000172:deficiency; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D003470:Culture Media; D007375:Interleukin-1; D012333:RNA, Messenger; D014212:Tretinoin; D002118:Calcium; D006854:Hydrocortisone