Altered expression and function of P-glycoprotein in dextran sodium sulfate-induced colitis in mice

Hisashi Iizasa, Naomi Genda, Tomohide Kitano, Mikio Tomita, Kazuyo Nishihara, Masahiro Hayashi, Kayako Nakamura, Shizuko Kobayashi, Emi Nakashima

研究成果: Article

34 引用 (Scopus)

抄録

P-glycoprotein (P-gp), the product of the multiple drug resistance (mdr) gene, can actively pump toxic drugs out of cells, but its pathophysiologic role is not yet fully understood. In this study, we examined the expression of P-gp in dextran sodium sulfate (DSS)-induced colitis in mice. Eight-week-old Balb/c female mice were given drinking water containing 7% DSS ad libitum for 7 days. Mice receiving DSS were sacrificed on days 3, 5, and 7 for histopathologic study. Tissue samples were examined by hematoxylin and eosin (HE) staining, and immunostained against mdr, CD4+, CD8+, and B220+. RNA was isolated from the large intestine and the expression of mdr1a was determined by RT-PCR. The function of P-gp was evaluated by rhodamine123 efflux using the everted sac method. The induction of colitis in mice was confirmed by body weight changes, HE staining and immunohistological grading of the large intestine with reference to CD4+, CD8+, and B220+ after 7 days of treatment. Severe inflammation was observed in the large, but not the small, intestine on day 7. The expression of mdr1a in the large intestine was reduced on days 3, 5, and 7. In addition, the P-gp function and the expression of PXR were also reduced in the large intestine of DSS-treated mice on day 3. This reduction was consistent with the immunohistologic observations. The expression of the mdr1a gene was reduced before severe symptoms appeared. These results suggest that P-gp expression may be related to the pathology of colitis.

元の言語English
ページ(範囲)569-576
ページ数8
ジャーナルJournal of Pharmaceutical Sciences
92
発行部数3
DOI
出版物ステータスPublished - 2003 3 1

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Dextran Sulfate
P-Glycoprotein
Colitis
Large Intestine
Multiple Drug Resistance
Hematoxylin
Eosine Yellowish-(YS)
Genes
Pharmaceutical Preparations
Staining and Labeling
Body Weight Changes
Poisons
Pathology
Drinking Water
Small Intestine
Pumps
RNA
Tissue
Inflammation
Gene Expression

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

これを引用

Iizasa, H., Genda, N., Kitano, T., Tomita, M., Nishihara, K., Hayashi, M., ... Nakashima, E. (2003). Altered expression and function of P-glycoprotein in dextran sodium sulfate-induced colitis in mice. Journal of Pharmaceutical Sciences, 92(3), 569-576. https://doi.org/10.1002/jps.10326

Altered expression and function of P-glycoprotein in dextran sodium sulfate-induced colitis in mice. / Iizasa, Hisashi; Genda, Naomi; Kitano, Tomohide; Tomita, Mikio; Nishihara, Kazuyo; Hayashi, Masahiro; Nakamura, Kayako; Kobayashi, Shizuko; Nakashima, Emi.

:: Journal of Pharmaceutical Sciences, 巻 92, 番号 3, 01.03.2003, p. 569-576.

研究成果: Article

Iizasa, H, Genda, N, Kitano, T, Tomita, M, Nishihara, K, Hayashi, M, Nakamura, K, Kobayashi, S & Nakashima, E 2003, 'Altered expression and function of P-glycoprotein in dextran sodium sulfate-induced colitis in mice', Journal of Pharmaceutical Sciences, 巻. 92, 番号 3, pp. 569-576. https://doi.org/10.1002/jps.10326
Iizasa, Hisashi ; Genda, Naomi ; Kitano, Tomohide ; Tomita, Mikio ; Nishihara, Kazuyo ; Hayashi, Masahiro ; Nakamura, Kayako ; Kobayashi, Shizuko ; Nakashima, Emi. / Altered expression and function of P-glycoprotein in dextran sodium sulfate-induced colitis in mice. :: Journal of Pharmaceutical Sciences. 2003 ; 巻 92, 番号 3. pp. 569-576.
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AU - Nishihara, Kazuyo

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AB - P-glycoprotein (P-gp), the product of the multiple drug resistance (mdr) gene, can actively pump toxic drugs out of cells, but its pathophysiologic role is not yet fully understood. In this study, we examined the expression of P-gp in dextran sodium sulfate (DSS)-induced colitis in mice. Eight-week-old Balb/c female mice were given drinking water containing 7% DSS ad libitum for 7 days. Mice receiving DSS were sacrificed on days 3, 5, and 7 for histopathologic study. Tissue samples were examined by hematoxylin and eosin (HE) staining, and immunostained against mdr, CD4+, CD8+, and B220+. RNA was isolated from the large intestine and the expression of mdr1a was determined by RT-PCR. The function of P-gp was evaluated by rhodamine123 efflux using the everted sac method. The induction of colitis in mice was confirmed by body weight changes, HE staining and immunohistological grading of the large intestine with reference to CD4+, CD8+, and B220+ after 7 days of treatment. Severe inflammation was observed in the large, but not the small, intestine on day 7. The expression of mdr1a in the large intestine was reduced on days 3, 5, and 7. In addition, the P-gp function and the expression of PXR were also reduced in the large intestine of DSS-treated mice on day 3. This reduction was consistent with the immunohistologic observations. The expression of the mdr1a gene was reduced before severe symptoms appeared. These results suggest that P-gp expression may be related to the pathology of colitis.

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