Lysophosphatidic acid up-regulates IL-10 production to inhibit TNF-α synthesis in MÏs stimulated with LPS.
J Leukoc Biol
; 106(6): 1285-1301, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31335985
Bacterial LPS strongly induces pro-inflammatory responses of MÏs after binding to CD14 protein and the TLR4/MD-2 receptor complex. The LPS-triggered signaling can be modulated by extracellular lysophosphatidic acid (LPA), which is of substantial importance for MÏ functioning under specific pathophysiological conditions, such as atherosclerosis. The molecular mechanisms of the crosstalk between the LPS- and LPA-induced signaling, and the LPA receptors involved, are poorly known. In this report, we show that LPA strongly inhibits the LPS-induced TNF-α production at the mRNA and protein levels in primary MÏs and MÏ-like J774 cells. The decreased TNF-α production in LPA/LPS-stimulated cells is to high extent independent of NF-κB but is preceded by enhanced expression and secretion of the anti-inflammatory cytokine IL-10. The IL-10 elevation and TNF-α reduction are both abrogated upon depletion of the LPA5 and LPA6 receptors in J774 cells and can be linked with LPA-mediated activation of p38. We propose that the binding of LPA to LPA5 and LPA6 fine-tunes the LPS-induced inflammatory response by activating p38, and up-regulating IL-10 and down-regulating TNF-α production.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lisofosfolípidos
/
Lipopolisacáridos
/
Factor de Necrosis Tumoral alfa
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Interleucina-10
/
Macrófagos
Límite:
Animals
Idioma:
En
Revista:
J Leukoc Biol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
Reino Unido