The IL-1 system in psoriatic skin: IL-1 antagonist sphere of influence in lesional psoriatic epidermis.
The epidermal expression of IL-1 in psoriasis is clearly altered, but data are still incomplete and poorly understood. To thoroughly study the IL-1 system in psoriasis, we semiquantitatively analyzed the expression of all currently characterized IL-1 isoforms and their receptors in parallel in both lesional (PP) and nonlesional psoriatic (PN) epidermis. Immunostaining of skin sections showed that IL-1alpha, located in the basal keratinocytes of normal control (NN) and PN epidermis, was significantly decreased to negligible levels in PP epidermis. IL-1 receptor antagonist (IL-1ra) and IL-1R type II (IL-1RII) were both significantly overexpressed in mutually exclusive compartments of PP epidermis, the suprabasal and basal compartment, respectively. A significant inverse correlation was found between the expressions of IL-1alpha and these two IL-1 antagonists, which may be inherent to the accelerated terminal differentiation of the psoriatic keratinocyte. In situ hybridization of IL-1(R) mRNAs confirmed the staining results. Levels of IL-1ra mRNA, however, were not increased in PP epidermis, suggesting that the overexpression of IL-1ra protein may be explained at the level of translation. The more sensitive PCR demonstrated a clearly increased expression of IL-1beta mRNA in PP epidermal cells (EC), which may be related to the inflammatory response in psoriasis. IL-1RI mRNA was clearly present in both PP and NN EC. The mRNA levels of the secreted IL-1ra isoform, but not intracellular IL-1raI and II, and IL-1RII were elevated in PP EC and paralleled those of IL-1beta. In summary, this study provides a defined phenotype of the complete epidermal IL-1 system in psoriasis; it shows that the expressions of IL-1(R) isoforms are coordinately altered, resulting in a predominance of IL-1 antagonists, which may represent a negative feedback response to IL-1 agonists, leading to a decreased IL-1 responsiveness.
Debets
R
R
Department of Dermatology, University Hospital Rotterdam-Dijkzigt, The Netherlands. Debets@immu.fgg.eur.nl
Hegmans
J P
JP
Croughs
P
P
Troost
R J
RJ
Prins
J B
JB
Benner
R
R
Prens
E P
EP
D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins