| Author | Carneiro, Alan Brito | |
| Author | Iaciura, Bruna Maria Ferreira | |
| Author | Nohara, Lilian Lie | |
| Author | Lopes, Carla Duque | |
| Author | Veas, Esteban Mauricio Cordero | |
| Author | Mariano, Vania Sammartino | |
| Author | Bozza, Patrícia T. | |
| Author | Lopes, Ulisses Gazos | |
| Author | Atelia, Georgia Correa | |
| Author | Almeida, Igor Correia | |
| Author | Silva Neto, Mário Alberto Cardoso | |
| Access date | 2015-09-28T13:02:39Z | |
| Available date | 2015-09-28T13:02:39Z | |
| Document date | 2013 | |
| Citation | CARNEIRO, Alan Brito; et al. Lysophosphatidylcholine Triggers TLR2- and TLR4- Mediated Signaling Pathways but Counteracts LPSInduced NO Synthesis in Peritoneal Macrophages by Inhibiting NF-κB Translocation and MAPK/ERK Phosphorylation. PLoS ONE, v.8, n.9, e76233, 9p, 2013. | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/11836 | |
| Language | eng | pt_BR |
| Publisher | Plos One | pt_BR |
| Rights | open access | |
| Title | Lysophosphatidylcholine Triggers TLR2- and TLR4- Mediated Signaling Pathways but Counteracts LPSInduced NO Synthesis in Peritoneal Macrophages by Inhibiting NF-κB Translocation and MAPK/ERK Phosphorylation | pt_BR |
| Type | Article | |
| DOI | 10.1371/journal.pone.0076233 | pt_BR |
| Abstract | Background: Lysophosphatidylcholine (LPC) is the main phospholipid component of oxidized low-density lipoprotein
(oxLDL) and is usually noted as a marker of several human diseases, such as atherosclerosis, cancer and diabetes.
Some studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However, effector molecules that are
present in oxLDL particles and can trigger TLR signaling are not yet clear. LPC was previously described as an
attenuator of sepsis and as an immune suppressor. In the present study, we have evaluated the role of LPC as a
dual modulator of the TLR-mediated signaling pathway.
Methodology/Principal Findings: HEK 293A cells were transfected with TLR expression constructs and stimulated
with LPC molecules with different fatty acid chain lengths and saturation levels. All LPC molecules activated both
TLR4 and TLR2-1 signaling, as evaluated by NF-қB activation and IL-8 production. These data were confirmed by
Western blot analysis of NF-қB translocation in isolated nuclei of peritoneal murine macrophages. However, LPC
counteracted the TLR4 signaling induced by LPS. In this case, NF-қB translocation, nitric oxide (NO) synthesis and
the expression of inducible nitric oxide synthase (iNOS) were blocked. Moreover, LPC activated the MAP Kinases
p38 and JNK, but not ERK, in murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in
peritoneal macrophages but not in TLR-transfected cells.
Conclusions/Significance: The above results indicate that LPC is a dual-activity ligand molecule. It is able to trigger
a classical proinflammatory phenotype by activating TLR4- and TLR2-1-mediated signaling. However, in the
presence of classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular responses, ultimately
inducing an anti-inflammatory phenotype; LPC may thus play a role in the regulation of cell immune responses and
disease progression. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA. | pt_BR |
| Affilliation | University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular Patogênicos. Ribeirão Preto, SP, Brasil. | pt_BR |
| Affilliation | University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA. | pt_BR |
| Affilliation | University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular Patogênicos. Ribeirão Preto, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Lysophosphatidylcholine | pt_BR |
| Subject | Peritoneal Macrophages | pt_BR |
| Subject | Phosphorylation | pt_BR |
| DeCS | Lipoproteínas | pt_BR |
| DeCS | Macrófagos Peritoneais | pt_BR |
| DeCS | Fosforilação | pt_BR |
