title: Culture medium from TNF-α-stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms.
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.
authors: 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.
authors: Wenru
authors: W
authors: Su
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Qian
authors: Q
authors: Wan
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Jingwen
authors: J
authors: Huang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Longhui
authors: L
authors: Han
authors: 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.
authors: Xiaoqing
authors: X
authors: Chen
authors: Center for Clinic Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China.
authors: Guihua
authors: G
authors: Chen
authors: Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pa.
authors: Nancy
authors: N
authors: Olsen
authors: 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.
authors: Song Guo
authors: SG
authors: Zheng
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: liangd631004@163.com.
authors: Dan
authors: D
authors: Liang
mesh_terms: D031164:Ambrosia / Q000737:chemistry / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D003228:Conjunctiva / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Allergy; B cells; allergic conjunctivitis; histamine; mast cells; mesenchymal stem cells; stems cells