Upregulation of interleukin-18 expression in mouse primary keratinocytes induced to differentiate by calcium

J Kong, Y Li - Archives of dermatological research, 2002 - Springer
J Kong, Y Li
Archives of dermatological research, 2002Springer
Interleukin-18 (IL-18) is an immunomodulatory cytokine that stimulates interferon-γ
production by T helper cells. Recently, basal keratinocytes have been shown to
constitutively express IL-18, and IL-18 expression increases in the suprabasal keratinocytes
in psoriatic lesions. In the study reported here we showed that in mouse epidermis, IL-18
immunoreactivity was markedly increased in the granular and cornified layers. To further
investigate whether differentiated keratinocytes synthesize more IL-18, we examined the …
Abstract
Interleukin-18 (IL-18) is an immunomodulatory cytokine that stimulates interferon-γ production by T helper cells. Recently, basal keratinocytes have been shown to constitutively express IL-18, and IL-18 expression increases in the suprabasal keratinocytes in psoriatic lesions. In the study reported here we showed that in mouse epidermis, IL-18 immunoreactivity was markedly increased in the granular and cornified layers. To further investigate whether differentiated keratinocytes synthesize more IL-18, we examined the expression of mouse IL-18 in primary mouse keratinocytes induced to differentiate by calcium, an in vitro cell culture system mimicking keratinocyte differentiation in the epidermis. We demonstrated that IL-18 mRNA and protein in cultured keratinocytes were increased by calcium treatment in a time- and dose-dependent manner. The upregulation of IL-18 was associated with an increase in keratinocyte differentiation markers, and was dependent on the synthesis of new RNAs and proteins. However, the IL-18 protein in the cytoplasm was predominantly in the precursor form, and no increase in IL-18 activity was detected in the culture medium treated with calcium. Furthermore, blocking the calcium-induced keratinocyte differentiation with protein kinase C inhibitor inhibited the upregulation of IL-18 expression. These findings suggest that IL-18 is synthesized in keratinocytes mainly in the inactive precursor form, and its expression is upregulated as basal keratinocytes differentiate in the epidermis.
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