Tags

Type your tag names separated by a space and hit enter

Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-κB and PPAR-γ.
Int Immunopharmacol. 2015 Feb; 24(2):314-324.II

Abstract

This study evaluated the influence of HIV protease inhibitors lopinavir/ritonavir (LPV/RTV) and atazanavir (ATV) on macrophage functions during their first interaction with Leishmania. Macrophages from BALB/c mice treated for 10days with LPV/RTV and ATV, infected or not in vitro with L. (L.) amazonensis, were used to investigate the effects of these drugs on infection index, leishmanicidal capacity, cytokine production and PPAR-γ and RelB expression. LPV/RTV and ATV treatments significantly increased the infection index and the percentage of Leishmania-infected macrophages compared to untreated infected macrophages. There was no correlated increase in the production of NO and H2O2 leishmanicidal molecules. Promastigotes derived from Leishmania-infected macrophages from LPV/RTV and ATV-treated BALB/c mice had an in vitro growth 45.1% and 56.4% higher in groups treated with LPV/RTV and ATV than with PBS in culture. ATV treatment reduced IL-12p70 and IL-10 secretion in Leishmania-infected macrophages, but had no effect on IL-23 and TNF production. LPV reduced IL-10 and had no effect on IL-12p70, TNF and IL-23 secretion. ATV treatment decreased PPAR-γ expression in Leishmania-infected macrophages compared to untreated infected macrophages. In addition, LPV/RTV, but not ATV, reduced RelB cytoplasm-to-nucleus translocation in Leishmania-infected macrophages. Results showed that LPV/RTV and ATV HIV protease inhibitors were able to modulate innate defense mechanisms against Leishmania via different intracellular pathways. Although HIV protease inhibitors are highly efficient to control the Human Immunodeficiency Virus, these drugs might also influence the course of leishmaniasis in HIV-Leishmania-co-infected individuals.

Authors+Show Affiliations

Laboratory of Cellular Immunology, Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil; Laboratory of Cellular and Molecular Immunology, René Rachou Research Center, Belo Horizonte, Minas Gerais, Brazil. Electronic address: erica.alves@cpqrr.fiocruz.br.Laboratory of Cellular Immunology, Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil. Electronic address: marthina.gomes@gmail.com.Laboratory of Cellular Immunology, Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil. Electronic address: tatianakarlab@gmail.com.Laboratory of Immunology and Inflammation, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasilia, Distrito Federal, Brazil. Electronic address: kellymagalhaes@unb.br.Laboratory of Cellular Immunology, Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil. Electronic address: mimjunqueira@unb.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25545854

Citation

Alves, Érica Alessandra Rocha, et al. "Anti-HIV Drugs, Lopinavir/ritonavir and Atazanavir, Modulate Innate Immune Response Triggered By Leishmania in Macrophages: the Role of NF-κB and PPAR-γ." International Immunopharmacology, vol. 24, no. 2, 2015, pp. 314-324.
Alves ÉAR, de Miranda MG, Borges TK, et al. Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-κB and PPAR-γ. Int Immunopharmacol. 2015;24(2):314-324.
Alves, É. A. R., de Miranda, M. G., Borges, T. K., Magalhães, K. G., & Muniz-Junqueira, M. I. (2015). Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-κB and PPAR-γ. International Immunopharmacology, 24(2), 314-324. https://doi.org/10.1016/j.intimp.2014.12.025
Alves ÉAR, et al. Anti-HIV Drugs, Lopinavir/ritonavir and Atazanavir, Modulate Innate Immune Response Triggered By Leishmania in Macrophages: the Role of NF-κB and PPAR-γ. Int Immunopharmacol. 2015;24(2):314-324. PubMed PMID: 25545854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-HIV drugs, lopinavir/ritonavir and atazanavir, modulate innate immune response triggered by Leishmania in macrophages: the role of NF-κB and PPAR-γ. AU - Alves,Érica Alessandra Rocha, AU - de Miranda,Marthina Gomes, AU - Borges,Tatiana Karla, AU - Magalhães,Kelly Grace, AU - Muniz-Junqueira,Maria Imaculada, Y1 - 2014/12/26/ PY - 2014/09/18/received PY - 2014/12/10/revised PY - 2014/12/15/accepted PY - 2014/12/30/entrez PY - 2014/12/30/pubmed PY - 2015/12/15/medline KW - Atazanavir KW - Cytokines KW - Leishmania KW - Lopinavir/ritonavir KW - PPAR-γ KW - RelB/NFκB SP - 314 EP - 324 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 24 IS - 2 N2 - This study evaluated the influence of HIV protease inhibitors lopinavir/ritonavir (LPV/RTV) and atazanavir (ATV) on macrophage functions during their first interaction with Leishmania. Macrophages from BALB/c mice treated for 10days with LPV/RTV and ATV, infected or not in vitro with L. (L.) amazonensis, were used to investigate the effects of these drugs on infection index, leishmanicidal capacity, cytokine production and PPAR-γ and RelB expression. LPV/RTV and ATV treatments significantly increased the infection index and the percentage of Leishmania-infected macrophages compared to untreated infected macrophages. There was no correlated increase in the production of NO and H2O2 leishmanicidal molecules. Promastigotes derived from Leishmania-infected macrophages from LPV/RTV and ATV-treated BALB/c mice had an in vitro growth 45.1% and 56.4% higher in groups treated with LPV/RTV and ATV than with PBS in culture. ATV treatment reduced IL-12p70 and IL-10 secretion in Leishmania-infected macrophages, but had no effect on IL-23 and TNF production. LPV reduced IL-10 and had no effect on IL-12p70, TNF and IL-23 secretion. ATV treatment decreased PPAR-γ expression in Leishmania-infected macrophages compared to untreated infected macrophages. In addition, LPV/RTV, but not ATV, reduced RelB cytoplasm-to-nucleus translocation in Leishmania-infected macrophages. Results showed that LPV/RTV and ATV HIV protease inhibitors were able to modulate innate defense mechanisms against Leishmania via different intracellular pathways. Although HIV protease inhibitors are highly efficient to control the Human Immunodeficiency Virus, these drugs might also influence the course of leishmaniasis in HIV-Leishmania-co-infected individuals. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/25545854/Anti_HIV_drugs_lopinavir/ritonavir_and_atazanavir_modulate_innate_immune_response_triggered_by_Leishmania_in_macrophages:_the_role_of_NF_κB_and_PPAR_γ_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(14)00503-7 DB - PRIME DP - Unbound Medicine ER -