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)-β1 signaling developed spontaneous lethal autoimmune inflammationand autoimmune diseases. Moreover, evidence for modified TGF-β 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-β type 1 receptor (TGF-βR1), 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 miceto 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-β1, TGF-βR1, latency-associated peptide (LAP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were assessed by ELISA. Moreover, the gene expression of TNF-α, IL-1β 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,dermatitisscore, ear thickness and scratching behavior. In parallel, SB-431542 blocked DNCB-induced elevation in serum levels of TNF-α, TGF-β1, TGF-βR1, LAP, IL-1β, IL-6 and IgE. The collective results indicate that SB-431542 partially suppresses DNCB-induced AD in micevia reduction of TGF-β1 signaling pathway associated with inhibition of inflammation and apoptosis.