TRAF6 as the Key Adaptor of TLR4 Signaling Pathway Is Involved in Acute Pancreatitis
2010 (English)In: PANCREAS, ISSN 0885-3177, Vol. 39, no 3, 359-366 p.Article in journal (Refereed) Published
Objectives: To study the potential role of tumor necrosis factor receptor-associated factor 6 (TRAF6) as the key adaptor of the toll-like receptor 4 (TLR4) signaling pathway in acute pancreatitis (AP) in mice. Methods: Acute pancreatitis was induced by 7 intraperitoneal injections of cerulein in TLR4-deficient (TLR4-Def) and TLR4 wild-type (TLR4-WT) mice. Inflammatory severity was scored and evaluated based on pathological study. TRAF6 expression was determined by reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry. Results: Acute pancreatitis was successfully induced in both mice strains, but the inflammatory progression was different. In TLR4-Def mice, pancreatic inflammation was blunt and mild first, then became increasingly intensive and peaked at the later stage, whereas in the TLR4-WT mice, the response was fast initiated and peaked at the early stage of AP, then alleviated gradually. TRAF6 expression in TLR4-Def mice was significantly higher than that in the TLR4-WT mice. Immunohistochemistry located TRAF6 expressed mainly in the pancreatic acinar cells. Conclusions: The TLR4-TRAF6 signaling pathway is critically involved in AP. Other signaling pathways beyond TLR4 may participate in the pancreatic inflammatory process via TRAF6. As a convergence point of the TLR4-dependent and the TLR4-independent signaling pathways, TRAF6 plays an important role in AP.
Place, publisher, year, edition, pages
2010. Vol. 39, no 3, 359-366 p.
acute pancreatitis, toll-like receptor 4, tumor necrosis factor receptor-associated factor 6
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-54771DOI: 10.1097/MPA.0b013e3181bb9073ISI: 000275955500011OAI: oai:DiVA.org:liu-54771DiVA: diva2:309850