The Expression And Mechanism Of IL-26in Psoriasis

BackgroundPsoriasis is a frequent, chronically relapsing, inflammatory skin diseasescharacterized by hyperproliferative keratinocytes and infiltration of T cells, dendriticcells, macrophages and neutrophils. The precise etiology for Psoriasis is not defined.Genetic, hormonal, environmental and infectious factors appear to play a critical rolein the pathogenesis of the disease. Psoriasis is currently considered as a T help cellsmediated autoimmune disease, cytokines and inflammatory cells play an importantrole in the pathogenesis of the disease. The proinflammatory cytokines TNF-ɑ, IL-1βand IL-6, produced by keratinocytes and infiltrating cells, participate to in thephysiopathology of psoriasis. The multiple proinflammatory cascades described inpsoriasis lead to persistent skin lesion inflammation. Although psoriasis has been firstconsidered as a Th1-mediated disease, the Th17cells have been recently reported toinvolve in psoriasis.IL-26, also known as AK155, produced by Th17cells，belongs to members of theIL-10cytokine family. The IL-26gene is conserved in most vertebrate species, but absent in most rodent strains (including mice and rat). IL-26was first discovered as agene in herpesvirus saimiri-transformed T cells. The expression of IL-26is restrictedto some T cell and NK cells. IL-26has been reported to signal via theIL-10R2/IL-20R1heterodimeric receptor. Although IL-10R2is broadly expressed,IL-20R1is only expressed by many epithelial cell types. IL-26has been found tooverexpress in Crohn’s disease and RA; And IL-26upregulates IL-8, IL-10, TNF-ɑ,and/or CD54expression by intestinal epithelial cell lines, associated to aphosphorylation of STAT3(and/or STAT1). However, the potential role of IL-26inhuman disease remains partially unknown.Objective:To examine expression of IL-26in serum from patients with psoriasis and itsmechanism in psoriasis, providing a clue for pathogenesis, diagnosis and therapy inpsoriasis.Methods:1. IL-26levels in serum were detected by ELISA and its correlation with PASI wasanalyzed.2. The effect of IL-26on STAT1phosphorylation in HaCaT cells was assayed byWestern Blot.3. Cytokines (TNF-α, IFN-γ and IL-1β) production by Keratinocytes followedstimulation of IL-26was tested by enzyme linked immunosorbent assay (ELISA).Results:1. Compared to healthy control group, the concentration of IL-26in serum wassignificantly higher in patients with Psoriasis（t=-15.63, P<0.001）and correlatedpositively with PASI （r=0.62, P<0.001） 2. IL-26induced phosphorylation of STAT1in HaCaT cells.3. The expression of TNF-α, IFN-γ and IL-1β in Keratinocytes were significantlyupregulated after IL-26stimulation(P<0.001).Conclusion：1. IL-26in serum was overexpressed in psoriasis and positively related to diseaseseverity.2. IL-26involved in pathogenesis of psoriasis through inducing phosphorylation ofSTAT1and cytokines (TNF-α, IFN-γ and IL-1β) production in keratinocytes.