The Mir-155/Gata3/Il37 Axis Modulates The Production Of Proinflammatory Cytokines Upon Tnf-Alpha Stimulation To Affect Psoriasis Development

Psoriasis is a recrudescent chronic immune-mediated inflammatory dermatosis; the production and release of proinflammatory cytokines/chemokines such as TNF-alpha has been regarded as critical issues during psoriasis pathogenesis. Based on online microarray profiles, the expression of the transcription factor GATA3 was downregulated in psoriasis lesion tissues. In the present study, we searched for miRNAs that might be related to TNF-alpha and GATA3 to investigate an in-depth understanding of psoriasis pathogenesis. Herein, higher TNF-alpha and GATA3 protein levels were observed in psoriasis lesion tissues and that GATA3 overexpression significantly reverses TNF-alpha-induced increases within the production of IL-6 and CXCL8 in keratinocytes. TNF-alpha stimulation increases miR-155 expression dose-independently, and the miR-155 inhibitor significantly reverses TNF-alpha-induced suppression of GATA3 protein levels and increases IL-6 and CXCL8 production. miR-155 could suppress the expression of GATA3 by targeting its 3 ' UTR, while GATA3 could activate the transcription of IL37 by targeting its promoter region. miR-155 overexpression reduces IL37 protein and increases CXCL8 production; GATA3 overexpression might significantly attenuate the effects of miR-155 overexpression. In contrast to GATA3, miR-155 expression is significantly upregulated in psoriasis lesion tissue and is negatively correlated with GATA3 and IL37. In summary, the miR-155/GATA3/IL37 axis modulates the production of IL-6 and CXCL8 upon TNF-alpha stimulation to affect psoriasis development. Thus, miR-155/GATA3/IL37 may be potent targets for psoriasis treatment, which needs further in vivo and clinical investigation.