Amphotericin B induces expression of genes encoding chemokines and cell adhesion molecules in the human monocytic cell line THP-1.
Amphotericin B is known to elicit immunomodulatory effects on neutrophil, monocyte, and lymphocyte function. It also has been shown to induce the release of proinflammatory cytokines from human monocytes and macrophages. Release of these cytokines has been associated with the infusion-related toxicity observed after administration of this drug. The present study demonstrates that amphotericin B increases mRNA for the chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1beta, as well as the cell adhesion molecules intercellular adhesion molecule (ICAM)-1 and CD44 in the human monocytic cell line THP-1. Amphotericin B increased the concentrations of IL-8, MCP-1, and MIP-1beta in a dose-dependent fashion. Amphotericin B also induced expression of ICAM-1 but not CD44 in these cells. Production of these proteins in response to amphotericin B may play a role in the immunomodulatory activity and toxicity of this antifungal agent.
Rogers
P D
PD
Dept. of Clinical Pharmacy Practice, School of Pharmacy, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. drogers@medicine.umsmed.edu
Stiles
J K
JK
Chapman
S W
SW
Cleary
J D
JD
D000666:Amphotericin B / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D009000:Monocytes; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D018960:Hyaluronan Receptors; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000666:Amphotericin B