Blocking TGF-β type 1 receptor partially reversed skin tissue damage in experimentally induced atopic dermatitis in mice

Animals with impaired transforming growth factor (TGF)-beta 1 signaling developed spontaneous lethal autoimmune inflammation and autoimmune diseases. Moreover, evidence for modified TGF-beta signaling in atopic dermatitis (AD) exists. Therefore, the goal of this study was to determine whether SB-431542, a potent and selective inhibitor of the TGF-beta type 1 receptor (TGF-[beta R1), could attenuate such a severe reaction in mice. In addition, the molecular underpinnings the possible protective effects were also investigated. Repeated epicutaneous application of DNCB was performed on the ear and shaved dorsal skin of mice to induce AD-like symptoms and skin lesions. SB-431542 (1 mg/kg) was given by intra-peritoneal injection three times weekly for 3 weeks to assess the anti-pruritic effects. Serum levels of TGF-beta 1, TOF beta R1, latency-associated peptide (LAP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 were assessed by ELISA. Moreover, the gene expression of TNF-alpha, IL-1 beta and IL-6 were determined. Apoptotic pathway was evaluated by measuring the activity of caspase-3 and by staining skin sections with anti-caspase-3 antibodies. We found that SB-431542 alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness and scratching behavior. In parallel, SS 431542 blocked DNCB-induced elevation in serum levels of TNF-alpha, TGF-beta 1, TGF-beta R1, LAP, IL-1 beta, IL-6 and IgE. The collective results indicate that SB-431542 partially suppresses DNCB-induced AD in mice via reduction of TGF-131 signaling pathway associated with inhibition of inflammation and apoptosis.