ArticleOpen biology2015
The human parasite Leishmania amazonensis downregulates iNOS expression via NF-κB p50/p50 homodimer: role of the PI3K/Akt pathway.
Article in Open biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- Topical application of ozonated sunflower oil accelerates the healing of lesions of cutaneous leishmaniasis in mice under meglumine antimoniate treatment.Medical microbiology and immunology · 2024Article
- Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.Frontiers in immunology · 2024Review
- MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis.Frontiers in genetics · 2023Article
- Toll-Like Receptor 3 (TLR3) Is Engaged in the Intracellular Survival of the Protozoan ParasiteInfection and immunity · 2022Article
- Transcriptomic Profile of Canine DH82 Macrophages Infected byInternational journal of molecular sciences · 2022Article
- Transcription Factors Interplay Orchestrates the Immune-Metabolic Response ofFrontiers in cellular and infection microbiology · 2021Review
- Innate Resistance toFrontiers in microbiology · 2021Article
- 14-3-3 Protein ofFrontiers in microbiology · 2019Article
- Considering Abundance, Affinity, and Binding Site Availability in the NF-κB Target Selection Puzzle.Frontiers in immunology · 2019Review
- The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes.Frontiers in cellular and infection microbiology · 2019Review
- Leishmania parasitophorous vacuole membranes display phosphoinositides that create conditions for continuous Akt activation and a target for miltefosine in Leishmania infections.Cellular microbiology · 2018Article
- Review
- Miransertib (ARQ 092), an orally-available, selective Akt inhibitor is effective against Leishmania.PloS one · 2018Article
- PI3K signaling in Leishmania infections.Cellular immunology · 2016Review
- Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection.PLoS neglected tropical diseases · 2016Article
- Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages.PLoS computational biology · 2016Article
- RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Leishmania amazonensis Engages CD36 to Drive Parasitophorous Vacuole Maturation.PLoS pathogens · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania amazonensis activates the NF-κB transcriptional repressor homodimer (p50/p50) and promotes nitric oxide synthase (iNOS) downregulation. We investigated the role of PI3K/Akt in p50/p50 NF-κB activation and the effect on iNOS expression in L. amazonensis infection. The increased occupancy of p50/p50 on the iNOS promoter of infected macrophages was observed and we demonstrated that both p50/p50 NF-κB induction and iNOS downregulation in infected macrophages depended on PI3K/Akt activation. Importantly, the intracellular growth of the parasite was also impaired during PI3K/Akt signalling inhibition and in macrophages knocked-down for Akt 1 expression. It was also observed that the increased nuclear levels of p50/p50 in L. amazonensis-infected macrophages were associated with reduced phosphorylation of 907 Ser p105, the precursor of p50. Corroborating these data, we demonstrated the increased levels of phospho-9 Ser GSK3β in infected macrophages, which is associated with GSK3β inhibition and, consequently, its inability to phosphorylate p105. Remarkably, we found that the levels of pPTEN 370 Ser, a negative regulator of PI3K, increased due to L. amazonensis infection. Our data support the notion that PI3K/Akt activity is sustained during the parasite infection, leading to NF-κB 105 phosphorylation and further processing to originate p50/p50 homodimers and the consequent downregulation of iNOS expression.
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