title: Leishmania mexicana promastigotes down regulate JNK and p-38 MAPK activation: Role in the inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.
abstract: Dendritic cells (DC) are one of the principal host cells of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously shown that the infection of monocyte-derived dendritic cells (moDC) with Leishmania mexicana inhibits campthotecin-induced apoptosis. Nevertheless, the mechanisms involved in the inhibition of apoptosis of dendritic cells by Leishmania have not been established. Mitogen-activated protein kinases (MAPK) are key participants in the process of apoptosis and different species of Leishmania have been shown to regulate these kinases. In the present study, we analyzed the effect of L. mexicana promastigotes in the activation of JNK and p38 MAP kinase and their participation in the inhibition of apoptosis. The infection of moDC with L. mexicana promastigotes diminished significantly the phosphorylation of the MAP kinases JNK and p38. The inhibition of both kinases diminished DNA fragmentation, but in a major extent was the reduction of DNA fragmentation when JNK was inhibited. The capacity of L. mexicana promastigotes to diminish MAP kinases activation is probably one of the strategies employed to delay apoptosis induction in the infected moDC and may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, D. F., Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodríguez-González
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, D. F., Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Wilkins-Rodríguez
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, D. F., Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argueta-Donohué
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, D. F., Mexico.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Aguirre-García
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México 06726, D. F., Mexico. Electronic address: lgutierr@unam.mx.
authors.forename: Laila
authors.initials: L
authors.lastname: Gutiérrez-Kobeh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000469:parasitology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007894:Leishmania mexicana / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D002166:Camptothecin
keywords: Apoptosis; Dendritic cells; Leishmania mexicana; MAPK; Promastigotes