title: Hypodermin A, a potential agent for prevention of allogeneic acute rejection.
abstract: Immunosuppressive agents play an important role in the success of organ transplantation, however the chronic toxicity of these agents is a major issue over the long-term. Hypodermin A (HA) is an enzyme secreted by the larvae of Hypoderma lineatum (Diptera: Oestridae), and has been implicated in immunosuppression in cattle. Malassagne et al. have demonstrated that HA can degrade the C3 protein, and could be used to prevent hyperacute xenogeneic rejection. We found that overexpression of HA in RAW264.7 cells induced significant secretion of prostaglandin E2 (PGE2), which mediates a variety of innate and adaptive immune responses through four E-type prostanoid (EP) receptor subtypes (EP1-4). PGE2 is useful in the management of allogeneic acute rejection. In addition, we found that induction of PGE2 expression downregulates the expression of interferon (IFN)-γ and interleukin (IL)-2, and promotes the secretion of IL-10 in vitro through the EP4 receptor. It was previously shown that activation of IL-2 and IFN-γ is involved in allograft acute rejection. IL-10 is known to prevent inflammation, and can improve allograft survival rates. We concluded that besides preventing hyperacute xenogeneic rejection, HA might also be a potential therapeutic candidate for ameliorating acute rejection during allotransplantation.
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Renjin
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Xuzhou Central Hospital, Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Ankang
authors.initials: A
authors.lastname: Hu
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Lianlian
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: zxr1967@126.com.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000208:Acute Disease; D000818:Animals; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004175:Diptera / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D016207:Cytokines; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012697:Serine Endopeptidases; C030092:hypodermin; D015232:Dinoprostone
keywords: Allotransplantation; Hypodermin A; PGE(2); Transplant rejection