| First Author | Ichiki T | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 5 | Pages | 1811-22 |
| PubMed ID | 26813973 | Mgi Jnum | J:239266 |
| Mgi Id | MGI:5828055 | Doi | 10.1096/fj.201500117 |
| Citation | Ichiki T, et al. (2016) Modulation of leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products (RAGE). FASEB J 30(5):1811-22 |
| abstractText | Leukotriene B4 (LTB4) receptor 1 (BLT1), a high-affinity GPCR for LTB4, plays important roles in acute and chronic inflammatory diseases. Although the LTB4-BLT1 axis is known to promote inflammation, no studies have defined the binding proteins that modulate LTB4-BLT1 signaling. In this study, the receptor for advanced glycation end products (RAGE) interacted with BLT1 in human cervical epithelial HeLa cells. RAGE increased LTB4-BLT1-dependent ERK phosphorylation and inhibited LTB4-BLT1-dependent activation of NF-kappaB and up-regulation of proinflammatory cytokines and chemokines. RAGE-dependent inhibition of NF-kappaB was blunted by treatment with an MEK inhibitor, suggesting that RAGE suppresses LTB4-BLT1-dependent NF-kappaB signaling by enhancing the MEK-ERK pathway. Meanwhile, in a chemotaxis assay of mouse bone marrow-derived neutrophils, the velocity of LTB4-dependent neutrophil migration was attenuated by soluble RAGE, which is an inhibitory decoy protein for RAGE signaling, in a dose-dependent manner (0.2-5 mug/ml), or by RAGE deficiency. Furthermore, both LTB4-dependent ERK phosphorylation in neutrophils and LTB4-dependent neutrophil accumulation in a murine peritonitis model were significantly attenuated in RAGE-deficient mice compared with C57BL/6J wild-type mice, indicating that RAGE potentiates LTB4-dependent neutrophil migration by enhancing ERK phosphorylation. Our results demonstrate that RAGE interacts with BLT1 and modulates LTB4-BLT1 signaling through potentiation of the MEK-ERK pathway.-Ichiki, T., Koga, T., Okuno, T., Saeki K., Yamamoto, Y., Yamamoto, H., Sakaguchi, M., Yokomizo, T. Modulation of leukotriene B4 receptor 1 signaling by receptor for advanced glycation end products (RAGE). |
