지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 293 - 298 (6page)
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The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.
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참고문헌 (30)
참고문헌 신청
Akazawa, Y. / 2002 / Effect of interferons on P-glycoprotein-mediated rhodamine-123 effl ux in cultured rat hepatocytes / J. Pharm. Sci 91:2110~2115
Bauer, B. / 2007 / Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier / Mol. Pharmacol 71:667~675
Belliard, A. M. / 2004 / Effect of tumor necrosis factor-alpha and interferon-gamma on intestinal Pglycoprotein expression, activity, and localization in Caco-2 cells / J. Pharm. Sci 93:1524~1536
Cheshire, J. L. / 1997 / Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation / Mol. Cell Biol 17:6746~6754
Cornford, E. M. / 1985 / The blood /brain barrier, a dynamic regulatory interface / Mol. Physiol 7:219~259
Bauer, B. / 2007 / Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier / Mol. Pharmacol 71:667~675
Belliard, A. M. / 2004 / Effect of tumor necrosis factor-alpha and interferon-gamma on intestinal Pglycoprotein expression, activity, and localization in Caco-2 cells / J. Pharm. Sci 93:1524~1536
Cheshire, J. L. / 1997 / Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation / Mol. Cell Biol 17:6746~6754
Cornford, E. M. / 1985 / The blood /brain barrier, a dynamic regulatory interface / Mol. Physiol 7:219~259
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