The Cholesterol-Binding Antibiotic Nystatin Induces Expression of Macrophage Inflammatory Protein-1 in Macrophages

Abstract

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-1α and MIP-1β, however, upon exposure to nystatin, significantly elevated expression of MIP-1α and MIP-1β 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-1α and MIP-1β 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.

Lysine enhances the effect of amphotericin B against <italic>Candida albicans in vitro</italic>

“…Nystatin, a polyene antifungal antibiotic, is a cholesterol sequestering agent that alters the composition of the plasma membrane of eukaryotic cells [48]. However, its effect on cells is poorly investigated [48]. It was also found in our study that combination of lysine and nystatin also had an enhanced action, and this enhanced action was even stronger than the combination of AmB and lysine.…”

“…The tube turbidity test indicated that there was a significant enhancement interaction between caspofungin or nystatin and lysine. Nystatin, a polyene antifungal antibiotic, is a cholesterol sequestering agent that alters the composition of the plasma membrane of eukaryotic cells [48]. However, its effect on cells is poorly investigated [48].…”

Osmotic Effects Induced by Pore-Forming Agent Nystatin: From Lipid Vesicles to the Cell

“…Nystatin has been used in experiments investigating the electrical properties of different tight epithelia, such as mammalian urinary bladder and colon epithelia, which characterized the conductances of the nystatin transmembrane pores for Na + , K + and Cl - [20,21]. In addition, it was observed that nystatin influences many mammalian cellular functions, among others the different intracellular signaling processes induced through the caveolae-associated proteins [22,23]. …”

Mangosteen xanthones suppress hepatitis C virus genome replication

“…Immunofluorescence analysis was conducted as described previously [30]. Briefly, Bart79I cells were grown on coverslips with indicated dose to 70 % confluency for 3 days.…”