| First Author | Phongsisay V | Year | 2014 |
| Journal | Mol Immunol | Volume | 62 |
| Issue | 1 | Pages | 169-77 |
| PubMed ID | 25004110 | Mgi Jnum | J:347757 |
| Mgi Id | MGI:6851721 | Doi | 10.1016/j.molimm.2014.06.012 |
| Citation | Phongsisay V, et al. (2014) LMIR5 extracellular domain activates myeloid cells through toll-like receptor 4. Mol Immunol 62(1):169-77 |
| abstractText | LMIR5/CD300b is an activating immunoglobulin-like receptor whose extracellular domain (LMIR5-Fc) is constitutively released from immune cells. The release of LMIR5-Fc is augmented upon stimulation with TLR agonists. LMIR5-Fc is reported to possess inflammatory activity and amplify LPS-induced lethal inflammation; however, its action mechanism has not been clarified. This study was aimed to identify receptors for LMIR5-Fc. Using NF-kappaB reporter cells in human monocytes THP1, LMIR5-Fc was solely found to trigger NF-kappaB activation among various signaling receptors examined. In addition, an injection of LMIR5-Fc into the mouse peritoneal resulted in a rapid production of inflammatory mediators and an amplification of LPS activity. Moreover, LMIR5-Fc-induced cytokine production was markedly reduced in TLR4-deficient mouse macrophages. Using TLR4 reporter cells, the LMIR5-Fc sample that contained a trace amount of endotoxin under the sensitivity of reporter cells triggered a potent NF-kappaB activation. Furthermore, the inflammatory activity of LMIR5-Fc was completely lost by heating but unchanged by polymyxin B pretreatment. Using TLR4 fusion protein, TLR4 was found to interact specifically with LMIR5-overexpressing cells. Therefore, LMIR5-Fc is new inflammatory mediator and endogenous ligand of TLR4. This study provides an insight into the positive feedback mechanism of inflammation through TLR4-LMIR5-Fc axis. |
