Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration in cholestatic rats receiving biliary intervention.
OBJECTIVE
Biliary intervention may augment chemokine expression and inflammatory cell infiltration and aggravates liver injury in cholestatic rats. We tested the efficacy of glucocorticoid pretreatment to prevent the complications.


METHODS
A model of biliary intervention was established in rats without (sham) or with bile duct ligation (BDL). Before biliary intervention, rats were randomly assigned to receiving intravenous injection of dexamethasone (DX group) or normal saline (NS group). Plasma levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were measured with enzyme-linked immunosorbent assay, and liver messenger RNA of these chemokines was quantified with real-time quantitative reverse transcriptase-polymerase chain reaction. Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase, respectively.


RESULTS
By 3 hours after biliary intervention, plasma MCP-1 and MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3 hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes returned to baseline levels by 24 hours.


CONCLUSIONS
Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration, which may consequently alleviate liver injury in cholestatic rats receiving biliary intervention.
Hsieh
Chih-Sung
CS
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung 833, Taiwan.
Wang
Pei-Wen
PW
Lee
Shin-Ye
SY
Huang
Chao-Cheng
CC
Chang
Nyuk-Kong
NK
Chen
Ching-Mei
CM
Wu
Chia-Ling
CL
Wang
Hsiu-Chuan
HC
Chuang
Jiin-Haur
JH
D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors*; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D053331:Ectodysplasins; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011292:Premedication; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D048069:Tumor Necrosis Factors / Q000378:metabolism
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D053331:Ectodysplasins; D005938:Glucocorticoids; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D003907:Dexamethasone; D009195:Peroxidase