ABSTRACT
Background: Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity has a major issue for long-term treatment. One method to improve therapies and methods is the application of immunomodulatory agents from parasites such as Hypoderma lineatum. Hypodermin A (HA) is a serine esterase secreted by the larvae of Hypoderma lineatum, several studies demonstrated its immunosuppressive mechanism in vitro, and recently we discovered that HA inhibits the expression of interferon (IFN)-γ and interleukin (IL)-2 and activates IL-10 expression. Therefore, we hypothesized that it might be a potential agent used to block allograft rejections. However, most studies of the immunosuppressive mechanisms associated with HA were undertaken at the cellular level. In order to augment these studies, we evaluated the immunosuppressive effects of HA in vivo using an HA transgenic mouse model. Result: Our results revealed similar findings to those reported by in vitro studies, specifically that HA induced prostaglandin E2 expression, downregulated IFN-γ and IL-2 expression, and promoted IL-10 secretion via E-type prostanoid receptor 4. Additionally, we observed that HA overexpression inhibited lipopolysaccharide-induced TLR4 activation. These findings provide insight into a new potential agent capable of blocking graft rejection. Conclusion: Our founding suggested that HA-related treatment could be a promising option to improve the viability of grafts in human.
Subject(s)
Animals , Mice , Serine Endopeptidases/immunology , Diptera/enzymology , Diptera/immunology , Graft Rejection/immunology , Enzyme-Linked Immunosorbent Assay , Serine Endopeptidases/metabolism , Blotting, Western , Cytokines , Immunosuppression Therapy , Interleukins/antagonists & inhibitors , Interferons/antagonists & inhibitors , Interleukin-10/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Toll-Like Receptor 4 , Real-Time Polymerase Chain Reaction , Graft Rejection/enzymology , Graft Rejection/prevention & controlABSTRACT
This study investigated the expression of hemeoxygenase-1 (HO-1) in rats with acute lung rejection and its implication. A valid rat orthotopic left lung transplantation model (SD rat-->Wistar rat) was established by using an improved three-cuff anastomosis technique. The rats were divided into control group, CoPP (HO-1 inducer)-treated group and ZnPP (HO-1 inhibitor)- treated group. The severity of acute rejection was graded on the basis of the morphologic changes of the lung samples stained with HE. The expression of HO-1 protein in lung tissue was detected by using immunohistochemistry and Western blot, and HO-1 mRNA activity was assayed by RT-PCR. The results showed that the expression of HO-1 protein was significantly increased with the acute rejection grading in rats (P0.05). It was concluded that HO-1 protein might be involved in the pathological process of post-graft acute rejection. The expression of HO-1 protein was increased gradually with aggravation of acute rejection, and HO-1 protein might be used as an index to monitor acute rejection after lung transplantation.
Subject(s)
Graft Rejection/enzymology , Heme Oxygenase (Decyclizing)/genetics , Heme Oxygenase (Decyclizing)/metabolism , Lung Transplantation , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Rats, WistarABSTRACT
A maior complicação que pode limitar a evolução a longo prazo de um transplante cardíaco é o desenvolvimento de doença arterial coronariana. Esta forma de doença coronariana é distinta da doença coronariana aterosclerótica de pacientes não submetidos a transplante cardíaco. Evidências atuais, obtidas mediante a ecografia intravascular, demonstraram que a ocorrência de uma disfunção endotelial precoce, principalmente mediada pela expressão da isoforma induzível da óxido nítrico sintetase (iNOS) e associa-se com desenvolvimento de aterosclerose no aloenxerto durante o primeiro ano após o transplante. Esta revisão foi elaborada começando pelos conceitos básicos (descrição da enzima NOS e suas isoformas conhecidas; breve comparação entre elas), revisando-se, na seqüência, a disfunção endotelial coronariana pós-transplante cardíaco do ponto de vista específico da função enzimática da NOS. No transplante cardíaco a iNOS promove rejeição aguda, mas previne a crônica. A relação entre estes efeitos completamente opostos permanece desconhecida, sabendo-se que são mecanismos diferentes dependentes do tempo