title: Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells.
abstract: Apparently for the first time, the peripheral blood monocytes of individuals with active visceral leishmaniasis (VL) have been found to show reduced expression of interferon gamma receptor-1 (IFNGR1). Since interferon gamma is the main cytokine responsible for defence against leishmanial parasites, it was thought possible that effective antileishmanial drugs may up-regulate IFNGR1. Confocal microscopy confirmed that monocytes from VL patients who had been treated, with sodium antimony gluconate (SAG), did display IFNGR1 up-regulation. To see if this effect could be mimicked in vitro, IFNGR1 expression was investigated using a human macrophage cell line (THP1), northern blotting and confocal microscopy. When the THP1 cells were treated with SAG or pentamidine, their expression of the receptor was increased. This drug-induced up-regulation was more intense if the macrophages were infected with Leishmania donovani than if they were left uninfected. The possibility that at least some antileishmanial drugs act by up-regulating IFNGR1 expression needs to be explored further. A good model for investigating the mechanisms of action of antileishmanial drugs might be based on the THP1 cell line.
authors.affiliation: Department of Immunology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Calcutta - 700 032, India.
authors.forename: B
authors.initials: B
authors.lastname: Dasgupta
authors.forename: K
authors.initials: K
authors.lastname: Roychoudhury
authors.forename: S
authors.initials: S
authors.lastname: Ganguly
authors.forename: P
authors.initials: P
authors.lastname: Kumar Sinha
authors.forename: S
authors.initials: S
authors.lastname: Vimal
authors.forename: P
authors.initials: P
authors.lastname: Das
authors.forename: S
authors.initials: S
authors.lastname: Roy
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D015152:Blotting, Northern / Q000379:methods; D002460:Cell Line; D002648:Child; D005260:Female; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010419:Pentamidine / Q000627:therapeutic use*; D017471:Receptors, Interferon / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
chemical_list: D000967:Antimony Sodium Gluconate; D000981:Antiprotozoal Agents; D010419:Pentamidine; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor