BAY 11-7082 inhibits the NF-kB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis.

BAY 11-7082 antagonizes I-B kinase-β preventing nuclear translocation of NF-B; it also inhibits NLRP3 inflammasome activation.NF-B is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20 mg/kg/i.p.) or its vehicle (100 μl/i.p of 0.9% NaCl). Skin of IMQ animals developed erythema, scales, thickening and epidermal acanthosis. IMQ skin samples showed increased expression of pNF-B and NLRP3 activation. BAY 11-7082 blunted epidermal thickness, acanthosis and inflammatory infiltrate. BAY 11-7082 reduced pNF-B, NLRP3, TNF-α, IL-6 and IL-1ß expression, blunted the phosphorylation of STAT-3 and decreased IL-23 levels. In addition, BAY 11-7082 reawakened the apoptotic machinery.NLRP3 KO animals showed a reduced total histological score but persistent mild acanthosis, dermal thickness and expression of pNF-B and pSTAT-3, following IMQ application.Our data suggest that BAY 11-7082 might represent an interesting approach for the management of psoriasis-like dermatitis depending on a dual inhibition of NF-kB and NLRP3.
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research