TRAF6 as the key adaptor of TLR4 signaling pathway is involved in acute pancreatitis.
OBJECTIVE
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.
Zhou
Xiang-Yu
XY
Department of General Surgery, Institute of Digestive Surgery, West China Hospital, Sichuan University, Sichuan, 610041 People's Republic of China.
Zhou
Zong-Guang
ZG
Ding
Jun-Li
JL
Wang
Ling
L
Wang
Rong
R
Zhou
Bing
B
Gu
Jun
J
Sun
Xiao-Feng
XF
Li
Yuan
Y
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D048029:TNF Receptor-Associated Factor 6; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D002108:Ceruletide