Anti-inflammatory effects of AhR agonist benvitimod in TNFα/IFNγ stimulated HaCaT cells and peripheral blood mononuclear cells from patients with atopic dermatitis

Abstract Background Benvitimod is a newly synthesized non-steroidal small molecule targeting the aryl hydrocarbon receptor(AhR). Clinical studies have demonstrated its efficacy for patients with psoriasis and atopic dermatitis(AD). Objectives To evaluate the therapeutic effects of benvitimod on peripheral blood mononuclear cells (PBMCs) and tumor necrosis factor α (TNFα)/interferon γ (IFNγ) stimulated human keratinocytes (HaCaT). Materials & Methods PBMCs were obtained from 6 patients with AD. PBMCs and HaCaT cells were cultured and the effects of benvitimod on cell viability were evaluated. The expression of inflammatory cytokines and chemokines in PBMCs and HaCaT cells was measured and the nuclear translocation of AhR in HaCaT cells was visualized. Reverse transcription quantitative polymerase chain reaction(RT-PCR) and western-blot(WB) were performed to detect the expression of cytochrome P4501A1(CYP1A1), filaggrin (FLG), involucrin (IVL) and thymic stromal lymphopoietin (TSLP) in HaCaT cells. Phosphorylation of STAT1 was determined by western-blot. Results Our research demonstrated that the cell proliferation of PBMCs and HaCaT cells were suppressed by benvitimod in a dose dependent manner. Benvitimod significantly suppressed TNFα/IFNγ(TI)-induced cytokine secretion and upregulated the expression of FLG and IVL in HaCaT cells. In addition, benvitimod induced the nuclear staining of AhR and inhibited the phosphorylation of STAT1 in HaCaT cells. Conclusion Benvitimod inhibited inflammatory effects in PBMCs of AD patients and underpinned the barrier-repairing effects by targeting AhR and STAT1 in TI-stimulated HaCaT cells. Benvitimod may be a potential therapeutic drug for inflammatory skin diseases such as AD.