Wenru Su1, Qian Wan2, Jingwen Huang2, Longhui Han2, Xiaoqing Chen3, Guihua Chen4, Nancy Olsen5, Song Guo Zheng6, Dan Liang7. 1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; Center for Clinic Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, 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; Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pa. 4. Center for Clinic Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China. 5. Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pa. 6. Center for Clinic Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China; Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pa. Electronic address: szheng1@hmc.psu.edu. 7. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: liangd631004@163.com.
Abstract
BACKGROUND: The immunomodulatory and anti-inflammatory functions of mesenchymal stem cells (MSCs) have been demonstrated in several autoimmune/inflammatory diseases, but their contribution to allergic conjunctivitis and underlying antiallergic mechanisms remain elusive. OBJECTIVE: We sought to explore the clinical application of MSCs to experimental allergic conjunctivitis (EAC) and its underlying antiallergic mechanisms. METHODS: Culture medium from TNF-α-stimulated, bone marrow-derived MSCs (MSC-CMT) was administered topically to mice with EAC, and the related allergic symptoms and biological changes were evaluated. Murine spleen-derived B cells, bone marrow-derived mast cells (MCs), and lung vascular endothelial cells were cultured in vitro to investigate the antiallergic MSC-CMT mechanisms. RESULTS: Topical instillation of MSC-CMT significantly attenuated the clinical symptoms of short ragweed pollen-induced EAC, with a significant decrease in inflammatory cell frequency, nuclear factor κB p65 expression, and TNF-α and IL-4 production. In vitro MSC-CMT significantly inhibited the activation of MCs and B-cell IgE release and reduced histamine-induced vascular hyperpermeability. During EAC, MSC-CMT treatment also decreased IgE production, histamine release, enrichment and activation of MCs, and conjunctival vascular hyperpermeability. The MSC-CMT-mediated inhibition of B cells, MCs, and histamine and its antiallergic effects during EAC were abrogated when MSCs were pretreated with COX2 small interfering RNA. CONCLUSIONS: Our findings provide compelling evidence that MSC-CMT inhibits EAC through COX2-dependent multiple antiallergic mechanisms and support the use of MSC-CMT as a novel strategy for treating allergic conjunctivitis.
BACKGROUND: The immunomodulatory and anti-inflammatory functions of mesenchymal stem cells (MSCs) have been demonstrated in several autoimmune/inflammatory diseases, but their contribution to allergic conjunctivitis and underlying antiallergic mechanisms remain elusive. OBJECTIVE: We sought to explore the clinical application of MSCs to experimental allergic conjunctivitis (EAC) and its underlying antiallergic mechanisms. METHODS: Culture medium from TNF-α-stimulated, bone marrow-derived MSCs (MSC-CMT) was administered topically to mice with EAC, and the related allergic symptoms and biological changes were evaluated. Murine spleen-derived B cells, bone marrow-derived mast cells (MCs), and lung vascular endothelial cells were cultured in vitro to investigate the antiallergic MSC-CMT mechanisms. RESULTS: Topical instillation of MSC-CMT significantly attenuated the clinical symptoms of short ragweed pollen-induced EAC, with a significant decrease in inflammatory cell frequency, nuclear factor κB p65 expression, and TNF-α and IL-4 production. In vitro MSC-CMT significantly inhibited the activation of MCs and B-cell IgE release and reduced histamine-induced vascular hyperpermeability. During EAC, MSC-CMT treatment also decreased IgE production, histamine release, enrichment and activation of MCs, and conjunctival vascular hyperpermeability. The MSC-CMT-mediated inhibition of B cells, MCs, and histamine and its antiallergic effects during EAC were abrogated when MSCs were pretreated with COX2 small interfering RNA. CONCLUSIONS: Our findings provide compelling evidence that MSC-CMT inhibits EAC through COX2-dependent multiple antiallergic mechanisms and support the use of MSC-CMT as a novel strategy for treating allergic conjunctivitis.
Authors: Antonio J Villatoro; Viviana Fernández; Silvia Claros; Cristina Alcoholado; Manuel Cifuentes; Jesús Merayo-Lloves; José A Andrades; José Becerra Journal: Int J Mol Sci Date: 2017-10-28 Impact factor: 5.923