Biomol Ther.  2013 Jan;21(1):42-48.

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

• Baek S
• Kim SM
• Lee SA
• Rhim BY
• Eo SK
• Kim K

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-1alpha and MIP-1beta, however, upon exposure to nystatin, significantly elevated expression of MIP-1alpha and MIP-1beta 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-1alpha and MIP-1beta 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.

Keyword

Nystatin; Macrophages; MIP-1

MeSH Terms

Cell Membrane
Chemokine CCL3
Chemokine CCL4
Cholesterol
Eukaryotic Cells
Macrophage Inflammatory Proteins*
Macrophages*
Nystatin*
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Phosphotransferases
Protein Kinase C
Chemokine CCL3
Chemokine CCL4
Cholesterol
Macrophage Inflammatory Proteins
Nystatin
Phosphotransferases
Protein Kinase C
p38 Mitogen-Activated Protein Kinases