Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms

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...

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Published in:Journal of allergy and clinical immunology 2015-08, Vol.136 (2), p.423-432.e8
Main Authors: Su, Wenru, MD, PhD, Wan, Qian, MD, Huang, Jingwen, MD, Han, Longhui, MD, Chen, Xiaoqing, MD, Chen, Guihua, MD, PhD, Olsen, Nancy, MD, Zheng, Song Guo, MD, PhD, Liang, Dan, MD, PhD
Format: Article
Language:English
Subjects:
allergic conjunctivitis
Allergy
Allergy and Immunology
Ambrosia - chemistry
Ambrosia - immunology
Animals
B cells
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Bone Marrow Cells - drug effects
Bone Marrow Cells - immunology
Bone Marrow Cells - pathology
Capillary Permeability - drug effects
Capillary Permeability - immunology
Cell Differentiation
Conjunctiva - drug effects
Conjunctiva - immunology
Conjunctiva - pathology
Conjunctivitis, Allergic - chemically induced
Conjunctivitis, Allergic - drug therapy
Conjunctivitis, Allergic - genetics
Conjunctivitis, Allergic - immunology
Culture Media, Conditioned - pharmacology
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - immunology
Gene Expression Regulation
histamine
Histamine - metabolism
Immunoglobulin E - genetics
Interleukin-4 - genetics
Interleukin-4 - immunology
mast cells
mesenchymal stem cells
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - immunology
Mesenchymal Stromal Cells - pathology
Mice
Mice, Inbred BALB C
Pollen - immunology
Primary Cell Culture
RNA, Small Interfering - genetics
RNA, Small Interfering - immunology
Signal Transduction
stems cells
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - pharmacology
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Summary: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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2014.12.1926