title: Azithromycin and spiramycin induce anti-inflammatory response in human trophoblastic (BeWo) cells infected by Toxoplasma gondii but are able to control infection.
abstract: Toxoplasma gondii is an important pathogen which may cause fetal infection if primary infection. Our previous studies have used human choriocarcinoma trophoblastic cells (BeWo cell line) as experimental model of T. gondii infection involving placental microenvironment. This study aimed to examine the effects of azithromycin and spiramycin against T. gondii infection in BeWo cells. Cells were treated with different concentrations of the macrolide antibiotics and analyzed first for cell viability using thiazolyl blue tetrazole (MTT) assay. As cell viability was significantly decreased with drug concentrations higher than 400 μg/mL, the concentration range used in further experiments was from 50 to 400 μg/mL. The number of infected cells and intracellular replication of T. gondii decreased after treatment with each drug. The infection induced up-regulation of the macrophage migration inhibitory factor (MIF), which was also enhanced in infected cells after treatment with azithromycin, but not with spiramycin. Analysis of the cytokine profile showed increase TNF-α, IL-10 and IL-4 production, but decreased IFN-γ levels, were detected in infected cells and treated with each drug. In conclusion, treatment of human trophoblastic BeWo cells with with azithromycin or spiramycin is able to control the infection and replication of T. gondii. In addition, treatment with these macrolides, especially with azityromycin induces an anti-inflammatory response and high MIF production, which can be important for the establishment and maintenance of a viable pregnancy during T. gondii infection.
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, 38405-320 Uberlândia, MG, Brazil. pribio85@hotmail.com
authors: P S
authors: PS
authors: Franco
authors: A O
authors: AO
authors: Gomes
authors: B F
authors: BF
authors: Barbosa
authors: M B
authors: MB
authors: Angeloni
authors: N M
authors: NM
authors: Silva
authors: A
authors: A
authors: Teixeira-Carvalho
authors: O A
authors: OA
authors: Martins-Filho
authors: D A O
authors: DA
authors: Silva
authors: J R
authors: JR
authors: Mineo
authors: E A V
authors: EA
authors: Ferro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D011247:Pregnancy; D015572:Spiramycin / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D014327:Trophoblasts / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D015572:Spiramycin; D017963:Azithromycin