Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1823, Issue 7, Pages 1192-1198Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2012.05.004
Keywords
SR-A; TLR4; LPS; Macrophage; NF-kappa B
Categories
Funding
- NIH [HL071837, GM083016, GM53552, GM093878]
Ask authors/readers for more resources
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 15 mm in the presence or absence of fucoidan (the SR-A ligand). The levels of phosphorylated I kappa B alpha (p-I kappa B alpha) were examined by Western blot. We observed that Poly I:C and LPS alone, but not Pam2CSK4 or fucoidan increased the levels of p-IKI3rx. However, LPS-induced increases in p-IKBa levels were further enhanced when presence of the fucoidan. lmmunoprecipitation 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 15 mm in the presence and absence of fucoidan. We observed that LPS-stimulated TNFa and IL-1 beta production was further enhanced in the WI' macrophages, but did not in either TLR4(-/-) or SR-A(-/-) macrophages, when fucoidan was present. Similarly, in the presence of fucoidan, LPSinduced IKBa phosphorylation, NF-kappa B 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. (C) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available