Role of triggering receptor expressed on myeloid cells-1 in experimental severe acute pancreatitis.
OBJECTIVE
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a regulator of immunity and an amplifier of inflammatory signaling. The aim was to clarify the role of TREM-1 in the pathophysiology of experimental severe acute pancreatitis (SAP).


METHODS
SAP was induced by retrograde injection of 3 and 20% sodium deoxycholate (DCA) into the biliopancreatic ducts in rats (DCA pancreatitis). Soluble TREM-1 levels in serum, ascitic fluid, pancreas, liver and kidney were determined with an established available enzyme-linked immunosorbent assay (ELISA) kit. To clarify the source of soluble TREM-1 in serum and ascitic fluid, peritoneal macrophage depletion was done. Moreover, the effect of blockade of TREM-1 pathway was examined using LP17 (a synthetic TREM-1 inhibitor).


RESULTS
Soluble TREM-1 levels in serum and ascitic fluid were higher in SAP. Membrane-bound TREM-1 protein was increased in pancreas, liver and kidney in SAP. Peritoneal macrophage depletion resulted in the reduction of soluble TREM-1 levels in serum and ascitic fluid. Pretreatment with LP17 improved the hepatic and renal dysfunction (serum aspartate aminotransferase and blood urea nitrogen levels) in SAP.


CONCLUSIONS
TREM-1 may act as an important mediator for inflammation and organ injury in SAP. TREM-1 may be a potential therapeutic target for the development of SAP and associated organ dysfunction.
Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama, 589-8511, Japan.
Keiko
K
Kamei
Takeo
T
Yasuda
Takashi
T
Ueda
Fu
F
Qiang
Yoshifumi
Y
Takeyama
Hitoshi
H
Shiozaki
D000208:Acute Disease; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D003840:Deoxycholic Acid / Q000009:adverse effects; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D010179:Pancreas / Q000737:chemistry; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D011971:Receptors, Immunologic; C547511:TREM1 protein, rat; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D003840:Deoxycholic Acid