HO-1 Induction Attenuates Imiquimod-induced Psoriasiform Inflammation By Negative Regulation Of Stat3 Signalig

Heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, has been found playing an important role in skin injury and wound healing, however, its function in cutaneous inflammatory disease, such as psoriasis, was not known. Stat3, a known transcription factor that induces inflammation and regulate cell differentiation, play a key role for the pathogenesis development of psoriasis. Targeting Stat3 may be potentially therapeutic in the treatment of psoriasis. In this paper, we found that activation of HO-1 significantly alleviated the disease related pathogenesis abnormality and then we further address the mechanism why HO-1 exert this immune protection. Our result show that upon HO-1 activator administration or HO-1 over expression, the Th17 related cytokines IL6/IL22 induced Stat3 activation were significantly suppressed, these accompanied with decreased cell proliferation and reverse the abnormal cell proliferation, and very interestingly, our result showed that HO-1 induced Stat3 suppression was mediated through the activation of Protein Tyrosine Phosphatase SHP-1. Our study provide direct evidence showing that HO-1 might be an useful therapeutic target for psoriasis, SHP-1 mediated suppression of Stat3 activation after HO-1 activation might represents a unique molecular mechanisms for regulation of Stat3 activation.