Illicium verum extract suppresses IFN-γ-induced ICAM-1 expression via blockade of JAK/STAT pathway in HaCaT human keratinocytes

Abstract Ethnopharmacological relevance Interferon-gamma (IFN-γ) signaling in keratinocytes plays an important role in mediating inflammatory conditions such as psoriasis and contact dermatitis. Illicium verum Hook. f. has been used in traditional medicine for treating skin inflammation, rheumatism, asthma, and bronchitis in Asia. Aim of the study To investigate the anti-inflammatory effects and regulatory mechanisms of Illicium verum extract (IVE) in the human keratinocyte cell line HaCaT. Materials and Methods In this study, we examined the effect of IVE on IFN-γ-induced ICAM-1 expression in HaCaT cells. The levels of IFN-γ receptor α (IFN-γRα), phosphorylated Janus kinase 2 (pJak2), phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and suppressor of cytokine signaling 1 (SOCS1) were analyzed by western blot. Expression of intercellular adhesion molecule-1 (ICAM-1) on the HaCaT cells was determined by reverse transcription-polymerase chain reaction, western blot, and cell-surface enzyme-linked immunosorbent assay. The effects of IVE and its constituents on the adherence of T lymphocytes to IFN-γ-treated HaCaT cells were also investigated. Results IVE significantly inhibited IFN-γ-induced mRNA and protein expression of ICAM-1. IVE inhibited IFN-γ-induced IFN-γRα, pJak2 and pSTAT1 expression in HaCaT cells. The expression of SOCS1 was up-regulated by treatment of IVE. In addition, IVE and its constituents (p-anisaldehyde and trans-anethole) effectively suppressed IFN-γ-induced adherence of Jurkat T cells to HaCaT cells and ICAM-1 expression on the cell surface. Conclusions These results indicate that the anti-inflammatory effects of IVE may contribute to therapeutic efficacy in IFN-γ-dependent inflammatory skin diseases by modulating the IFN-γ signal pathway.