부산대학교 도서관

Background: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of [NAD.sup.+]/NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-[kappa]B and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of [NAD.sup.+] levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of [NAD.sup.+]/NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice. Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-[kappa]B p65 and STAT3 was determined by Western blotting. Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the [NAD.sup.+]/NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23. Conclusion: Pharmacological modulation of cellular [NAD.sup.+] levels could be a promising therapeutic approach for psoriasis-like skin disease. Keywords: psoriasis, NQO1, [NAD.sup.+], SIRT1, inflammatory cytokine
Introduction Psoriasis is a chronic, immune-mediated, inflammatory skin disease characterized by hyperproliferative keratinocytes, parakeratosis, hyperkeratosis, and massive infiltration of inflammatory cells. (1) Although the pathogenesis of psoriasis is not fully [...]