Roles of Islet Toll-Like Receptors in Pig to Mouse Islet Xenotransplantation

Autor: Han Ro, Eun Won Lee, Joo Ho Hong, Kyu Hyun Han, Hye-Jung Yeom, Hwa Jung Kim, Myung-Gyu Kim, Hye Seung Jung, Kook-Hwan Oh, Kyong Soo Park, Curie Ahn, Jaeseok Yang
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Cell Transplantation, Vol 22 (2013)
Druh dokumentu: article
ISSN: 0963-6897
1555-3892
DOI: 10.3727/096368912X657684
Popis: Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic/polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Both poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response and thereby contributed to xenograft rejection.
Databáze: Directory of Open Access Journals
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