Tofacitinib suppresses mast cell degranulation and attenuates experimental allergic conjunctivitis
Tofacitinib suppresses mast cell degranulation and attenuates experimental allergic conjunctivitis
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托法替尼抑制肥大细胞脱颗粒并减轻实验性过敏性结膜炎
DOI：
10.1016/j.intimp.2020.106737
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Liang, Dan
中科院分区：
文献类型：
--
作者：
Li, Yingqi;Liu, Xiuxing;Liang, Dan
Background: Allergic conjunctivitis (AC), a common eye inflammation that affects patients' health and quality of life, is still a therapeutic challenge for ophthalmologists. Tofacitinib, a new Janus kinase (JAK) inhibitor, has been successfully used in the treatment of several disorders. Nonetheless, its effect in AC and the potential anti-allergic mechanisms are still unclear. The objective of the current study was to explore the roles of tofacitinib in preventing AC and elucidate the potential underlying mechanisms.Methods: Tofacitinib was used topically in BALB/c mice with experimental allergic conjunctivitis (EAC). Ocular allergic symptoms and biological modifications were examined. To assess the anti-allergic mechanisms of tofacitinib, RBL-2H3 cells and HUVECs were cultured in vitro. The inhibitory effects and mechanisms of tofacitinib were studied and measured by real-time quantitative PCR, ELISA, western blot analysis, and flow cytometry.Results: Topical administration of tofacitinib reduced the clinical symptoms of OVA-induced EAC, with a substantial mitigation in inflammatory cell infiltration, histamine release, and TNF-alpha mRNA as well as IL-4 mRNA expression. In vitro, tofacitinib repressed the degranulation and cytokine production in RBL-2H3 cells and reduced histamine-induced vascular hyperpermeability. The underlying mechanism might involve the downregulation of phosphorylation of JAK3/STATs signaling molecules in RBL-2H3 cells and HUVECs.Conclusions: Our findings provide evidence that tofacitinib prevented EAC by targeting the JAK3/STATs pathway. We recommend the use of tofacitinib as an innovative approach for the treatment of AC.
