Abstract
The interleukin (IL)-1 family of cytokines includes IL-1α and IL-1β which are ubiquitous inducers of inflammation and other interleukins, that are expressed in a cell type-specific manner. Here, we investigated the expression of IL-1 family genes during terminal differentiation of normal human epidermal keratinocytes and the association of these genes with skin phenotypes during evolution. While IL1A and IL1B were downregulated, IL36 isoforms as well as IL37 and IL38 genes were strongly upregulated during differentiation of primary human keratinocytes. Western blot analysis showed that the anti-inflammatory cytokine IL-37 was highly abundant at the protein level in differentiated keratinocytes in vitro and in normal human epidermis where immunohistochemical staining revealed expression specifically in the granular layer. The IL36A, IL36B, IL37, and IL38 genes have been lost during the evolutionary degeneration of the epidermal cornification program in fully aquatic mammals. Our results suggest that the formation of a normal stratum corneum is associated with the expression of IL-1 family cytokines, including the anti-inflammatory protein IL-37.
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