| First Author | Yu H | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1823 |
| Issue | 7 | Pages | 1192-8 |
| PubMed ID | 22627090 | Mgi Jnum | J:185204 |
| Mgi Id | MGI:5427762 | Doi | 10.1016/j.bbamcr.2012.05.004 |
| Citation | Yu H, et al. (2012) Scavenger receptor A (SR-A) is required for LPS-induced TLR4 mediated NF-kappaB activation in macrophages. Biochim Biophys Acta 1823(7):1192-8 |
| abstractText | Recent evidence suggests that the macrophage scavenger receptor class A (SR-A, aka, CD204) plays a role in the induction of innate immune and inflammatory responses. We investigated whether SR-A will cooperate with Toll-like receptors (TLRs) in response to TLR ligand stimulation. Macrophages (J774/a) were treated with Pam2CSK4, (TLR2 ligand), Polyinosinic:polycytidylic acid (Poly I:C) (TLR3 ligand), and Lipopolysaccharides (LPS) (TLR4 ligand) for 15min in the presence or absence of fucoidan (the SR-A ligand). The levels of phosphorylated IkappaBalpha (p-IkappaBalpha) were examined by Western blot. We observed that Poly I:C and LPS alone, but not Pam2CSK4 or fucoidan increased the levels of p-IkappaBalpha. However, LPS-induced increases in p-IkappaBalpha levels were further enhanced when presence of the fucoidan. Immunoprecipitation and double fluorescent staining showed that LPS stimulation promotes SR-A association with TLR4 in the presence of fucoidan. To further confirm our observation, we isolated peritoneal macrophages from SR-A deficient (SR-A(-/-)), TLR4(-/-) and wild type (WT) mice, respectively. The peritoneal macrophages were treated with LPS for 15min in the presence and absence of fucoidan. We observed that LPS-stimulated TNFalpha and IL-1beta production was further enhanced in the WT macrophages, but did not in either TLR4(-/-) or SR-A(-/-) macrophages, when fucoidan was present. Similarly, in the presence of fucoidan, LPS-induced IkappaBalpha phosphorylation, NF-kappaB binding activity, and association between TLR4 and SR-A were significantly enhanced in WT macrophages compared with LPS stimulation alone. The data suggests that SR-A is needed for LPS-induced inflammatory responses in macrophages. |
