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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 42 - 48 (7page)
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Nystatin, a polyene antifungal antibiotic, is a cholesterol sequestering agent. The antifungal agent alters composition of the plasma membrane of eukaryotic cells, whereas its effects on cells are poorly investigated. In the current study, we investigated the question of whether nystatin was able to induce expression of macrophage inflammatory protein-1 (MIP-1). THP-1 cells rarely express MIP-$1{\alpha}$ and MIP-$1{\beta}$, however, upon exposure to nystatin, significantly elevated expression of MIP-$1{\alpha}$ and MIP-$1{\beta}$ was observed in a dose-dependent fashion at the messenger and protein levels. Cellular factors activated by nystatin as well as involved in nystatin-induced expression of MIP-1 proteins were identified in order to understand the molecular mechanisms of action of the anti-fungal agent. Treatment with nystatin resulted in enhanced phosphorylation of Akt, ERK, p38 MAPK, and JNK. Abrogation or significant attenuation of nystatin-induced expression of MIP-$1{\alpha}$ and MIP-$1{\beta}$ was observed by treatment with Akt inhibitor IV, LY294002, and SP6001250. Inhibition of ERK or p38MAPK using U0126 and SB202190 did not lead to attenuation of MIP-1 expression. In addition, inhibitors of protein kinase C, such as GF109203X and Ro-318220, also attenuated expression of MIP-1. These results indicate that nystatin is able to activate multiple cellular kinases and, among them, Akt and JNK play primary roles in nystatin-induced expression of MIP-1 proteins.
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참고문헌 (32)
참고문헌 신청
Blanpain, C. / 2001 / A chimeric MIP-1alpha/RANTES protein demonstrates the use of different regions of the RANTES protein to bind and activate its receptors / J. Leukoc. Biol 69:977~985
Bolard, J. / 1986 / How do the polyene macrolide antibiotics affect the cellular membrane properties? / Biochim. Biophys. Acta 864:257~304
Brown, D. A. / 1998 / Functions of lipid rafts in biological membranes / Annu. Rev. Cell Dev. Biol 14:111~136
Chen, X. / 2001 / Activation of mitogen-activated protein kinase by membrane-targeted Raf chimeras is independent of raft localization / J. Biol. Chem 276:34617~34623
Chi, H. / 2006 / Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses / Proc. Natl. Acad. Sci. USA 103:2274~2279
Bolard, J. / 1986 / How do the polyene macrolide antibiotics affect the cellular membrane properties? / Biochim. Biophys. Acta 864:257~304
Brown, D. A. / 1998 / Functions of lipid rafts in biological membranes / Annu. Rev. Cell Dev. Biol 14:111~136
Chen, X. / 2001 / Activation of mitogen-activated protein kinase by membrane-targeted Raf chimeras is independent of raft localization / J. Biol. Chem 276:34617~34623
Chi, H. / 2006 / Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses / Proc. Natl. Acad. Sci. USA 103:2274~2279
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