title: Synthesis and secretion of interleukin-1 alpha and interleukin-1 receptor antagonist during differentiation of cultured keratinocytes.
abstract: Keratinocytes produce interleukin-1 alpha (IL-1 alpha) and the epithelial variant of its inhibitor, interleukin-1 receptor antagonist (icIL-1ra). Both IL-1 alpha and icIL-1ra lack a secretory signal peptide; however, some icIL-1ra is found in the supernatants of cultured keratinocytes. The lack of correlation with the release of the cytosolic enzyme lactate dehydrogenase suggests that icIL-1ra can be actively secreted. Brefeldin A fails to block icIL-1ra release, suggesting that this protein may be externalized by keratinocytes through a leaderless pathway of secretion. Only minute amounts of soluble extracellular IL-1 alpha are detected: however, both IL-1 alpha and icIL-1ra can be released from the external face of the keratinocyte plasma membrane by mild acidic treatment, suggesting that IL-1 alpha can also be secreted by keratinocytes. The observation of membrane-associated IL-1 alpha and icIL-1ra might reflect an autocrine loop of regulation. Support for this hypothesis comes from the finding that keratinocytes, when exposed to exogenous recombinant IL-1 alpha, increase their content in both IL-1 alpha and IL-1ra mRNA. When keratinocytes are subjected to counterflow centrifugal elutriation, three major cell populations are obtained, representing three different degrees of keratinocyte differentiation. Cells from all populations synthesize IL-1 alpha and IL-1ra: however, while IL-1 alpha is uniformly distributed in cells from all maturational stages, IL-1ra accumulates in large, more differentiated keratinocytes. Changes in the ratio of IL-1ra to IL-1 alpha production and secretion by keratinocytes at different degrees of maturation might contribute to the control of growth and differentiation of human skin.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, University of Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corradi
authors.forename: A T
authors.initials: AT
authors.lastname: Franzi
authors.forename: A
authors.initials: A
authors.lastname: Rubartelli
mesh_terms: D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins