Scavenger Receptor A (SR-A) is Required for LPS-Induced TLR4 Mediated NF-κB Activation in Macrophages
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 IκBα (p-IκBα) were examined by Western blot. We observed that Poly I:C and LPS alone, but not Pam2CSK4 or fucoidan increased the levels of p-IκBα. However, LPS-induced increases in p-IκBα 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 TNFα and IL-1β 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 IκBα phosphorylation, NF-κB 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.
Yu, Honghui; Ha, Tuanzhu; Liu, Li; Wang, Xiaohui; Gao, Ming; Kelley, Jim; Kao, Race; Williams, David; and Li, Chuanfu. 2012. Scavenger Receptor A (SR-A) is Required for LPS-Induced TLR4 Mediated NF-κB Activation in Macrophages. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1823(7). 1192-1198. https://doi.org/10.1016/j.bbamcr.2012.05.004 PMID: 22627090 ISSN: 0167-4889