| Background:Psoriasis is a commonly occurring inflammatory skin disorder and is characterized by over-proliferation and disturbed differentiation of keratinocytes.Although the pathogenesis of psoriasis is not fully understood,it is widely accepted that cytokines play a key role in both emergence and maintenance of psoriatic lesions.Numerous immune mediators play been described as being elevated in the diseased skin of these patients,such as IL-6,IL-8,IL-12,TNF,IFN-?,which can be up-regulated by IL-19.IL-19 is mainly produced by keratinocytes,IL-19 induces the secretion of KGF from CD8+ T cells.The elevating expression of IL-19 in keratinocytes relates to IL-1? stimulation.As well as,staphylococcus aureus infection induced IL-1? production in an ?-toxin-dependent mechanism in nutrophils.A growing number of researchers believe that infection is one of the important factors in psoriasis development and progression.Staphylococcus aureus(S.aureus)is detected in about 50% of skin lesions in patients with psoriasis and is associated with a higher Psoriasis Area Severity Index(PASI)score.S.aureus affects the host immune system by producing pathogenic molecules and toxins.It has also been reported that ?-toxin can target keratinocytes and is related to AD disease severity,but the relationship between the ?-toxin and psoriasis remains unclear.Thus,we hypothesized that ?-toxin hemolysin promotes IL-1? expression in neutrophils,and then IL-1? enhances IL-19 production in keratinocytes.?-toxin secreted by staphylococcus aureus was involved in the development and progression of psoriasis.Objective:The present study aimed to explore the mechanism that ?-toxin produced by staphylococcus aureus promoted the expression of IL-19 in the keratinocytes.Preliminary study on the mechanism and the relationship between the development and progression of psoriasis and ?-toxin,for understanding the pathogenesis of psoriasis to provide certain theoretical experimental basis.Methods:1.qRT-PCR was employed to quantify the expression level of IL-19 in the in psoriatic skin and healthy skin.Western blotting was employed to detect ?-toxin in culture media of S.aureus isolated from the skin of healthy controls(HC)and psoriasis patients.Analysis the correlation between the expression level of IL-19 and secretion level of ?-toxin.2.The BALB/c mice were infected with ?Hla S.aureus,WT S.aureus,or PBS at days 1,3,7 after infection,HE staining was employed to evaluate the Inflamatory lesion,and the IL-19 and IL-1? mRNA and protein levels were detected by qRT-PCR and ELISA.Mouse Neutrophils were isolated from bone marrow and stimulated with ?Hla S.aureus,WT S.aureus,or meida,and the IL-1? expression level was detected by qRT-PCR,Western blot and ELISA;PAM 2-12 mouse keratinocytes were stimulated with different doses IL-1?,and the IL-19 mRNA and protein levels were detected by qRT-PCR and ELISA.Results:1.IL-19 mRNA expression in skin lesion of 80 psoriasis patients is significantly higher than the expression levels in skin tissues of 40 healthy individuals(1.708±0.1610 VS 0.5679± 0.0978;P<0.05).2.The staphylococcus aureus infection rate in skin lesion of psoriasis patients is significantly higher than that in skin tissues of healthy individuals(P<0.05).The positive rate of ?-toxin secretion by staphylococcus aureus in skin lesion of psoriasis patients is significantly higher than that in skin tissues of healthy individuals(P<0.05).3.The IL-19 mRNA expression levels were significantly correlation with ?-toxin secretion by staphylococcus aureus in skin lesion of psoriasis patients(r=0.7999,P<0.0001).4.The inflammatory cells infiltration and abscess formation were less in ?Hla S.aureus group than those in the WT S.aureus.5.The IL-19 and IL-1? mRNA and protein levels were significantly lower in ?Hla S.aureus group than those in the WT S.aureus group(P<0.01).6.In vitro,the IL-1? expression in mouse neutrophils stimulated with ? Hla S.aureus was significantly lower than those stimulated with WT S.aureus(P<0.01);7.In vitro,the IL-19 expression in PAM 2-12 keratinocytes stimulated with IL-1? was significantly increased in a dose-dependent manner(P<0.01).Conclusion:?-toxin produced by staphylococcus aureus promotes IL-1? expression in neutrophils,and then IL-1? enhances IL-19 production in keratinocytes.?-toxin secreted by staphylococcus aureus was involved in the development and progression of psoriasis. |
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