title: Prostaglandin E2 and Transforming Growth Factor-β Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells.
abstract: BACKGROUND
  The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs) remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2) inhibitor or transforming growth factor-β (TGF-β) neutralizing antibodies.
  
  
  RESULTS
  Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-β neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and lung draining lymph nodes (LLNs). ASCs engraftment caused significant increases in the regulatory T cell (Treg) and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-β eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.
  
  
  CONCLUSIONS
  ASCs are capable of secreting PGE2 and TGF-β, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors responsible for suppressing allergic airway inflammation.
authors.affiliation: Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
authors.forename: Kyu-Sup
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Hak-Sun
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Hwan-Jung
authors.initials: HJ
authors.lastname: Roh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D018793:Interleukin-13; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone