Interleukin 1 receptor antagonist in human epidermis and cultured keratinocytes

Abstract

Inter&kin 1 (IL-l), 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-lra) was analyzed in human skin, sweat and cultured keratinocytes. Extracts of both skin and cultured keratinocytes blocked the binding of ['2sI]IL-1 to its receptor whereas sweat did not. The inhibitory activity was cell-associated, was not secrctcd by cultured keratinocytes, and IL-lra mRNA was identified in these cells. There was an inverse relationship between the level of IL-lra and that of IL-la andj3 since extracts of differentiating kerdtinocytes (DK) and higher IL-lra levels and expressed more mRNA for IL-lra than non-differentiated keratinocytcs (NDK), whereas NDK contained 4 times more IL-la and /? 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-I in normal and inflamed human skin

Regulation of Interleukin-1α Expression by Integrins and Epidermal Growth Factor Receptor in Keratinocytes from a Mouse Model of Inflammatory Skin Disease

“…1). The decrease in Erk activity is consistent with the described role of Erk in maintaining proliferation and inhibiting differentiation of keratinocytes (5,19,25,26), and the decline in IL-1␣ levels supports earlier observations that IL-1␣ expression decreases during keratinocyte differentiation both in vitro and in vivo (27)(28)(29). In contrast, icIL-1ra tended to accumulate along with differentiation markers such as the cornified envelope precursor cornifin ( Fig.…”

IL-1 receptor antagonist in saliva; characterization in normal saliva and reduced concentration in Sjo¨gren's syndrome (SS)

“…However, epithelial cells from cornea were recently reported to produce the secreted form of IL-1Ra [9], which concurs with our results. The increasing concentration of IL-1Ra with increasing differentiation of mucosal cells parallels findings in keratinocytes [27] and suprabasal cells of cornea [9]. IL-1Ra could play a part in this process and in apoptosis, its final stage [28].…”

Modulation of the IL-1 cytokine network in keratinocytes by intracellular IL-1α and IL-1 receptor antagonist

“…By contrast, confluent cultures of HaCAT cells produce less IL-la and have a higher iclL-lRa:IL-la ratio (248: 1), which is of a similar order of magnitude to that reported for normal skin in vivo [9]. Diflerentiating keratinocytes, as found in confluent cultures, have previously been reported to contain higher IL-IRa levels, and non-differentiated keratinocytes higher IL-ln levels [6]. Using confluent cultures of HaCAT cells, we found that TGF-a, IFN-7.…”

“…Keratinocytes make only lhe intracellular form of IL-IRa which is not secreted, since icIL-IRa lacks the required leader sequence for transport into the Golgi apparatus. However, this icIL-lRa is released together with IL-lo on disruption of keratinocyte membranes [5,6]. Thus the net proinflammatory effect of the IL-1 cytokine network in diseased or damaged skin reflects the balance between the concentrations of IL-la.…”