6-6OAS Prostaglandin E2 and Transforming Growth Factor-β Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells

Thursday, 15 October 2015: 16:45 - 17:00
Room R2 ABC (Floor 3) (Coex Convention Center)

Sue Jean Mun , Pusan National University Yangsan Hospital, Busan, South Korea

Hwan-Jung Roh , MD, PhD, South Korea

Kyu-Sup Cho , Pusan National University, Busan, South Korea

Hak-Sun Yu , MD, PhD, South Korea

Mi-Kyung Park , MD, PhD, South Korea

Hee-Young Park , MD, South Korea

Sung-Lyong Hong , MD, PhD, South Korea

Background: To know the major soluble factors responsible for immunomodulatory effects of adipose-derived stem cells (ASCs) in an asthmatic mouse, we evaluated the effects of ASCs on allergic inflammation in the indoleamine 2,3-dioxygenase knockout (IDO-KO) mice and mice treated with prostaglandin E2 (PGE2) inhibitor and transforming growth factor-β (TGF-β) specific neutralizing antibodies.

Methods: ASCs were injected intravenously in wild-type (WT) and IDO-KO asthmatic mice. PGE2 inhibitor and TGF-β neutralizing antibodies were injected intraperitoneally on four consecutive days at the approximate time of ASCs injection. We investigated the immunomodulatory effects of ASCs between WT and IDO-KO mice, WT mice treated with and without PGE2 inhibitor, and WT mice treated with and without anti-TGF-β antibodies respectively.

Results: In WT and IDO-KO asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, 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 (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and lung draining lymph nodes (LLNs). Furthermore, ASCs engraftment caused significant increases the regulatory T cells (Tregs) and IL-10+ T cells populations in LLNs. However, when treating mice with PGE2 inhibitor and TGF-β neutralizing antibodies, blocking PGE2 and TGF-β, but not IDO-KO mice, eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.

Conclusion: ASCs themselves are capable of secreting PGE2 and TGF-β, which may play a role in inducing Tregs expansion. Furthermore, PGE2 inhibitor and 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 in suppressing the allergic airway inflammation.