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Regulation of P‐gp Under Inflammatory Conditions in the BME‐UV In Vitro Model
Author(s) -
Albataineh Mohammad M.,
Schultz Bruce D.,
Merwe Deon,
Malreddy Pradeep,
Gehring Ronette
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1002.22
Subject(s) - p glycoprotein , tumor necrosis factor alpha , glycoprotein , epithelium , downregulation and upregulation , efflux , in vitro , inflammation , proinflammatory cytokine , messenger rna , gene expression , chemistry , biology , endocrinology , microbiology and biotechnology , immunology , gene , biochemistry , multiple drug resistance , genetics , antibiotics
P‐glycoprotein (efflux pump) belongs to the ATP‐binding cassette (ABC) super‐family that may influence the bioavailability and disposition of many drugs. Mammary secretory epithelium expresses different families of drug transport proteins, including P‐glycoprotein [1,2] . Results from functional studies suggest that P‐glycoprotein is expressed on the apical membrane of the mammary epithelium. During inflammatory reactions, which can be associated with changes in mammary epithelial barrier functions, pro‐inflammatory cytokines tumor necrosis factor alpha (TNF‐α) and interleukin‐6 (IL‐6) are elevated in milk and serum [3] . In this study, the role of TNF‐α in regulating P‐glycoprotein was investigated in cultured BME‐UV cells. The mRNA expression of ABCB1, the gene encoding for P‐glycoprotein, was upregulated after 48 and 72 h of exposure to TNF‐α. After 120 h, mRNA expression decreased but still higher than the control level. P‐glycoprotein expression followed the same trend as ABCB1 mRNA expression, increasing after 24, 48, 72 h of exposure to TNF‐α and then decreasing after 120 h. Transepithelial electrical resistance (Rte) was within 15% of the control value at all the time points, except 120 h, when it increased by 50%. These results suggest that expression levels of P‐glycoprotein may be altered by inflammation thereby affecting the movement of its substrates across mammary epithelial barrier.