Endotoxin Tolerance of RAW264.7 Correlates with p38-dependent Up-regulation of Scavenger Receptor-A  

Oleh:

Xiang, Q. ; Wen, L. ; Liu, M.H. ; Zhang, Y.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The Journal of International Medical Research vol. 37 no. 02 (Mar. 2009), page 491-502.
Topik: Endotoxin

Ketersediaan

Perpustakaan FK Nomor Panggil: J11.K.2009.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Pre-exposure to lipopolysaccharide (LPS) leads to hyposensitivity to secondary LPS stimulation, known as endotoxin tolerance. The role of macrophage scavenger receptor-A (SR-A) in endotoxin tolerance is unknown. In this study, LPS was shown to induce SR-A expression in the mouse macrophage cell line, RAW264.7, in dose- and time-dependent manners, which correlated with inflammatory cytokine suppression in RAW264.7 on secondary LPS stimulation. Over-expression of SR-A in RAW264.7 suppressed tumour necrosis factor (TNF)-alpha release and nuclear factor (NF)-kappa-B activation, demonstrating the involvement of SR-A in endotoxin tolerance. LPS-pre-treated RAW264.7 cells could bind and internalize more fluorescein isothiocyanate (FITC)–LPS than untreated cells and both the SR-A ligand, fucoidan, and anti-SR-A 2F8 antibodies completely suppressed LPS-induced binding and internalization of FITC–LPS by RAW264.7. LPS-induced SR-A expression on RAW264.7 was completely suppressed by the p38-specific inhibitor, SB203580, but not by inhibition of toll-like receptor 4 (TLR4) signalling with MTS510, demonstrating that p38- but not TLR4-dependent up-regulation of SR-A was involved in endotoxin tolerance through binding and internalization of LPS.

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