Relationship between expression of triggering receptor-1 on myeloid cells in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis

doi:10.5847/wjem.j.1920-8642.2011.03.011

Abstract

Abstract:

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane-bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP.
METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score.
RESULTS: The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P<0.01, P<0.05). The expression levels of TREM-1, IL-1β and TNF-α mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P<0.01, P<0.05). The expression level of TREM-1mRNA was positively correlated with IL-1β and TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-α mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group.
CONCLUSIONS: The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-l might play an important role in the development of intestinal barrier dysfunction in rats with SAP.

Key words: Severe acute pancreatitis, Triggering receptor expressed on myeloid cells-1, Intestinal barrier dysfunction, Tumor necrosis factor-α ;, Interleukin-1β

Kai Yin, Sheng-chun Dang, Jian-xin Zhang. Relationship between expression of triggering receptor-1 on myeloid cells in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis[J]. World Journal of Emergency Medicine, 2011, 2(3): 216-221.

Figures/Tables 9

Table 1

Table 2

Table 3

Table 4

Figure 1.

Table 5

Figure 2.

Figure 3.

Table 6

References 24

1	Nakajima T, Ueda T, Takeyama Y, Yasuda T, Shinzeki M, Sawa H, et al. Protective effects of vascular endothelial growth factor on intestinal epithelial apoptosis and bacterial translocation in experimental severe acute pancreatitis. Pancreas 2007; 34:410-416. doi: 10.1097/mpa.0b013e3180335c64 pmid: 17446839
2	Dang SC, Zhang JX, Qu JG, Mao ZF, Wang XQ, Zhu B. Dynamic changes of IL-2/IL-10, sFas and expression of Fas in intestinal mucosa in rats with acute necrotizing pancreatitis. World J Gastroenterol 2008; 14:2246-2250. doi: 10.3748/wjg.14.2246 pmid: 18407603
3	Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001; 410:1103-1107. doi: 10.1038/35074114 pmid: 11323674
4	Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266-1273. doi: 10.1038/ni1411 pmid: 17110943
5	Nathan C, Ding A. TREM-1: a new regulator of innate immunity in sepsis syndrome. Nat Med. 2001; 7:530-532. doi: 10.1038/87846 pmid: 11329047
6	Wang DY, Qin RY, Liu ZR, Gupta MK, Chang Q. Expression of TREM-1 mRNA in acute pancreatitis. World[J] Gastroenterol. 2004; 10:2744-2746.
7	Schenk M, Bouchon A, Seibold F, Mueller C. TREM-1-expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. J Clin Invest 2007; 117:3097-106.
8	Kamei K, Yasuda T, Ueda T, Qiang F, Takeyama Y, Shiozaki H. Role of triggering receptor expressed on myeloid cells-1 in experimental severe acute pancreatitis. J Hepatobiliary Pancreat Sci 2010; 17: 305-312. Epub 2009 Sep 29. doi: 10.1007/s00534-009-0191-6 pmid: 19787284
9	Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970; 101:478-483. doi: 10.1001/archsurg.1970.01340280030009 pmid: 5457245
10	Park JJ, Cheon JH, Kim BY, Kim DH, Kim ES, Kim TI, et al. Correlation of serum-soluble triggering receptor expressed on myeloid cells-1 with clinical disease activity in inflammatory bowel disease. Dig Dis Sci 2008; 54:1525-1531. doi: 10.1007/s10620-008-0514-5 pmid: 18975078
11	Tzivras M, Koussoulas V, Giamarellos-Bourboulis EJ, Tzivras D, Tsaganos T, Koutoukas P, et al. Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease. World J Gastroenterol 2006; 12:3416-3419. doi: 10.3748/wjg.v12.i21.3416 pmid: 16733861
12	González-Roldán N, Ferat-Osorio E, Aduna-Vicente R, Wong-Baeza I, Esquivel-Callejas N, Astudillo-de la Vega H, et al. Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery. World J Gastroenterol 2005; 11:7473-7479. doi: 10.3748/wjg.v11.i47.7473 pmid: 16437719
13	Ferat-Osorio E, Wong-Baeza I, Esquivel-Callejas N, Figueroa-Figueroa S, Duarte-Rojo A, Guzmán-Valdivia-Gómez G, et al. Triggering receptor expressed on myeloid cells-1 expression on monocytes is associated with inflammation but not with infection in acute pancreatitis. Crit Care 2009; 13:R69. doi: 10.1186/cc7876 pmid: 19442309
14	Morencos FC, de las Heras Castaño G, Martín Ramos L, López Arias MJ, Ledesma F, Pons Romero F. Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci 1995; 40:1252-1256. pmid: 7781442
15	Kitanaka J, Kitanaka N, Tsujimura T, Terada N, Takemura M. Expression of diamine oxidase (histaminase) in guinea-pig tissues. Eur J Pharmacol 2002; 437:179-185. doi: 10.1016/s0014-2999(02)01302-x pmid: 11890907
16	Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns 2004; 30:135-139. doi: 10.1016/j.burns.2003.09.032 pmid: 15019120
17	Zhang X-p, Zhang J, Song Q-l, Chen HQ. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier. J Zhejiang Univ Sci B 2007; 8:888-895. doi: 10.1631/jzus.2007.B0888 pmid: 18257123
18	Pereda J, Sabater L, Cassinello N, Gómez-Cambronero L, Closa D, Folch-Puy E, et al. Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases. Ann Surg 2004; 240:108-116. pmid: 15213626
19	Strobel O, Wachter D, Werner J, Uhl W, Müller CA, Khalik M, et al. Effect of a pneumoperitoneum on systemic cytokine levels, bacterial translocation, and organ complications in a rat model of severe acute pancreatitis with infected necrosis. Surgical Endoscopy 2006; 20:1897-903. doi: 10.1007/s00464-005-0417-x pmid: 17024542
20	Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003; 3:745-756. doi: 10.1038/nri1184 pmid: 12949498
21	Granger J, Remick D. Acute pancreatitis: models, markers, and mediators. Shock 2005; 24(Suppl 1):45-51. doi: 10.1097/01.shk.0000191413.94461.b0
22	Mole DJ, Taylor MA, McFerran NV, Diamond T. The isolated perfused liver response to a 'second hit' of portal endotoxin during severe acute pancreatitis. Pancreatology 2005; 5:475-485. doi: 10.1159/000086614 pmid: 15985775
23	Gong JP, Wu CX, Liu CA, Li SW, Shi YJ, Yang K, et al. Intestinal damage mediated by Kupffer cells in rats with endotoxemia. World J Gastroenterol 2002; 8:923-927. doi: 10.3748/wjg.v8.i5.923 pmid: 12378643
24	Leveau P, Wang X, Sun Z, Börjesson A, Andersson E, Andersson R. Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant. Biochemical Pharmacology 2005; 69:1325-1331. doi: 10.1016/j.bcp.2005.01.023

	Primer	PCR product (bp)
TREM-1	5'-AAGTATGCCAGAAGCAGGAAGG-3'	138
	5'-GGTAGGGTCATCTTTCAGGGTGT-3'
IL-1β	5'-AATACCACTTGTTGGCTTA-3'	130
	5'-TGTGATGTTCCCATTAGAC-3'
TNF-α	5'-CGTCGTAGCAAACCACCAAG-3'	426
	5'-CACAGAGCAATGACTCCAAAG-3'
β-actin	5'-CCTGTACGCCAACACAGTGC-3'	211
	5'-ATACTCCTGCTTGCTGATCC-3'

Group	n	Serum D-lactate
Group	n	2 h	6 h	12 h	24 h
SAP	8	3.884±0.320	5.992±0.403	10.722±1.307	7.004±0.649
SO	8	1.678±0.072	1.784±0.054	2.108±0.110	1.744±0.0594
P		<0.01	<0.01	<0.01	<0.01

Group	n	Serum DAO
Group	n	2 h	6 h	12 h	24 h
SAP	8	0.372±0.044	0.805±0.0785	1.046±0.115	0.733±0.044
SO	8	0.217±0.027	0.243±0.012	0.307±0.022	0.221±0.013
P		<0.05	<0.05	<0.05	<0.05

Group	n	Serum endotoxin
Group	n	2 h	6 h	12 h	24 h
SAP	8	0.346±0.034	0.477±0.023	0.540±0.030	0.604±0.011
SO	8	0.139±0.056	0.117±0.018	0.132±0.009	0.142±0.009
P		<0.05	<0.05	<0.05	<0.05

Group	TREM-1	IL-1β	TNF-α
SO	0.185±0.060	0.116±0.035	0.136±0.023
SAP 2 h	0.330±0.028^*	0.457±0.068^*	0.547±0.080^*
SAP 6 h	0.348±0.030^*	0.490±0.049^*	0.645±0.061^**
SAP 12 h	0.427±0.043^*	0.598±0.054^**	0.689±0.050^*
SAP 24 h	0.407±0.050^*	0.622±0.101^**	0.589±0.037^*