Interleukin 1 receptor antagonist in human epidermis and cultured keratinocytes.
Interleukin 1 (IL-1), present in high amounts in normal human skin without any sign of inflammation, suggests a complex mechanism by which its bioactivity is regulated. The specific receptor antagonist of IL-1 (IL-1ra) was analyzed in human skin, sweat and cultured keratinocytes. Extracts of both skin and cultured keratinocytes blocked the binding of [125I]IL-1 to its receptor whereas sweat did not. The inhibitory activity was cell-associated, was not secreted by cultured keratinocytes, and IL-1ra mRNA was identified in these cells. There was an inverse relationship between the level of IL-1ra and that of IL-1 alpha and beta since extracts of differentiating keratinocytes (DK) and higher IL-1ra levels and expressed more mRNA for IL-1ra than non-differentiated keratinocytes (NDK), whereas NDK contained 4 times more IL-1 alpha and beta proteins than DK. This association of cell differentiation with a shift in agonist/antagonist ratio might be related to important autocrine or paracrine functions of IL-1 in normal and inflamed human skin.
Gruaz-Chatellard
D
D
Department of Medicine, Hôpital Cantonal Universitaire, Genève, Switzerland.
Baumberger
C
C
Saurat
J H
JH
Dayer
J M
JM
D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D004817:Epidermis / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis* / Q000378:metabolism; D015603:Keratinocytes / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D013542:Sweat / Q000737:chemistry / Q000502:physiology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D012313:RNA