Yingqi Li1, Xiuxing Liu2, Jianfeng Yu3, Zhuang Li2, Yuxi Chen2, He Li2, Xiaoqing Chen2, Wenru Su4, Dan Liang5. 1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China. 2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. 3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; Medical School, Nantong University, Nantong, China; Eye Institute, Affiliated Hospital of Nantong University, Nantong, China. 4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: suwr3@mail.sysu.edu.cn. 5. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: liangdan@gzzoc.com.
Abstract
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-α 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.
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-α 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.
Authors: Jason R Burchett; Jordan M Dailey; Sydney A Kee; Destiny T Pryor; Aditya Kotha; Roma A Kankaria; David B Straus; John J Ryan Journal: Cells Date: 2022-09-27 Impact factor: 7.666