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.