| First Author | Ciesielska A | Year | 2019 |
| Journal | J Leukoc Biol | Volume | 106 |
| Issue | 6 | Pages | 1285-1301 |
| PubMed ID | 31335985 | Mgi Jnum | J:282098 |
| Mgi Id | MGI:6379158 | Doi | 10.1002/JLB.2A0918-368RR |
| Citation | Ciesielska A, et al. (2019) Lysophosphatidic acid up-regulates IL-10 production to inhibit TNF-alpha synthesis in Mvarphis stimulated with LPS. J Leukoc Biol 106(6):1285-1301 |
| abstractText | Bacterial LPS strongly induces pro-inflammatory responses of Mvarphis 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 Mvarphi 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-alpha production at the mRNA and protein levels in primary Mvarphis and Mvarphi-like J774 cells. The decreased TNF-alpha production in LPA/LPS-stimulated cells is to high extent independent of NF-kappaB but is preceded by enhanced expression and secretion of the anti-inflammatory cytokine IL-10. The IL-10 elevation and TNF-alpha 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-alpha production. |
