81000121

open access

Version of Record

Decreased Expression of Toll-like Receptor 2 and 4 on Macrophages in Experimental Severe Acute Pancreatitis

English (英語)

The Kobe journal of the medical sciences

53(5)

219-227

Kobe University School of Medicine

2007-01

2008-02-20

In severe acute pancreatitis (SAP), immunologic impairment in the early phase maybe linked to subsequent infectious complications that are main contributor to the highmortality. Toll-like receptors (TLRs) recognize microorganisms as the innate immunesystem, and are involved in host defense mechanism. TLR2 recognizes lipoteichoic acid(LTA) of gram-positive bacteria, and TLR4 recognizes lipopolysaccharide (LPS) ofgram-negative bacilli. This study aimed to investigate the expression of TLRs onmacrophages and their TLRs-mediated cytokine production in rat SAP. SAP wasinduced by retrograde injection of 3% sodium deoxycholate into the biliopancreaticduct in male Wistar rats. Macrophages were isolated from bronchoalveolar lavage fluid6 hours after induction of SAP. The expression of TLR2 and TLR4 was analyzed byreal-time RT-PCR and western blotting. TNF-α release from macrophages wasestimated after 4-hour stimulation of LTA or LPS. Endotoxin/bacterial translocation(E/BT) was also evaluated in this model. The expression of TLR2 (mRNA and protein)and LTA-mediated TNF-α production were significantly decreased in SAP comparedwith control. The expression of TLR4 (mRNA and protein) and LPS-mediated TNF-αproduction was also significantly decreased in SAP compared with control. E/BToccurred 18 hours after induction of SAP. These results suggest that the impairedresponsiveness to LTA and LPS of macrophages is derived from decreased expressionof TLR2 and TLR4, respectively. This suppression of immune response in the earlyphase may be implicated in the mechanism of infectious complications.

macrophage

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