Effect of lipopolysaccharide on peptide transporter 1 expression in rat small intestine and its attenuation by dexamethasone.
OBJECTIVE
The peptide transporter (PepT1) activity is upregulated or preserved under certain pathological conditions. The aim of this study was to investigate the PepT1 expression during lipopolysaccharide (LPS) treatment and the effect of dexamethasone on PepT1 expression.


METHODS
Rats were injected daily for 3 days with (1) LPS; (2) LPS plus dexamethasone; (3) dexamethasone, and (4) saline only. Mucosal specimens were used for Northern blot and Western blot analyses. Tissues of small intestine were taken for histological studies. In addition, tumor necrosis factor alpha and interleukin 1 beta levels were determined 3 h after single injections of the above mediators.


RESULTS
Northern blot analysis revealed that LPS treatment significantly decreased the expression of mRNA for PepT1 (32-62% of controls) at different time points. In the LPS + dexamethasone group, it was 66-95% of controls. The protein level of PepT1 in the jejunum was consistent with the mRNA expression level. Immunohistochemistry also showed a reduction of PepT1 immunoreactivity in the LPS group. LPS treatment resulted in increased tumor necrosis factor alpha and interleukin 1 beta levels, but dexamethasone treatment profoundly counteracted the cytokine production.


CONCLUSIONS
This is the first report that LPS treatment reduces PepT1 expression in the rat small intestine. Short-term treatment with dexamethasone attenuated the effects of LPS by decreasing the cytokine levels.
Shu
Hong-Jin
HJ
2nd Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan. shuhong@med.id.yamagata-u.ac.jp
Takeda
Hiroaki
H
Shinzawa
Haruhide
H
Takahashi
Tsuneo
T
Kawata
Sumio
S
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004151:Dipeptides / Q000096:biosynthesis; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters
D002352:Carrier Proteins; D004151:Dipeptides; D008070:Lipopolysaccharides; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; D027981:Symporters; D003907:Dexamethasone