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Suppression of lipopolysaccharide-induced inflammatory response by fragments from serum amyloid A
Zhou H.1; Chen M.1; Zhang G.1; Ye R.D.1
2017-08-01
Source PublicationJournal of Immunology
ISSN15506606 00221767
Volume199Issue:3Pages:1105-1112
AbstractSerum amyloid A (SAA) is known as an acute-phase protein and a biomarker for inflammatory diseases. Published studies have shown that SAA possesses proinflammatory cytokine-like activity and is chemotactic for phagocytes, but the structural basis for these activities remains unidentified. In this article, we report that truncated SAA1 proteins lacking N- and C-terminal sequences exhibit reduced proinflammatory activity and strongly suppress LPS-induced expression of IL-1β, IL-6, and TNF-α in macrophages. A truncated SAA1 containing aa 11-58 was examined further and found to facilitate p38 MAPK phosphorylation while reducing LPS-stimulated phosphorylation of ERK and JNK. In LPS-challenged mice, aa 11-58 reduced the severity of acute lung injury, with significantly less neutrophil infiltration in the lungs and attenuated pulmonary expression of IL-1β, IL-6, and TNF-α. Coadministration of aa 11-58 markedly improved mouse survival in response to a lethal dose of LPS. A potent induction of IL-10 was observed in a TLR2-dependent, but TLR4-independent, manner in macrophages stimulated with aa 11-58. However, the aa 11-58 fragment of SAA1 was unable to induce chemotaxis or calcium flux through formyl peptide receptor 2. These results indicate that the N- and C-terminal sequences contain structural determinants for the proinflammatory and chemotactic activities of SAA1, and their removal switches SAA1 to an anti-inflammatory role. Given that proteolytic processing of SAA is associated with the pathological changes in several diseases, including secondary amyloidosis, our findings may shed light on the structure- function relationship of SAA1 with respect to its role in inflammation.
DOI10.4049/jimmunol.1700470
URLView the original
Language英語
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shanghai Jiao Tong University
2.University of Macau
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GB/T 7714
Zhou H.,Chen M.,Zhang G.,et al. Suppression of lipopolysaccharide-induced inflammatory response by fragments from serum amyloid A[J]. Journal of Immunology,2017,199(3):1105-1112.
APA Zhou H.,Chen M.,Zhang G.,&Ye R.D..(2017).Suppression of lipopolysaccharide-induced inflammatory response by fragments from serum amyloid A.Journal of Immunology,199(3),1105-1112.
MLA Zhou H.,et al."Suppression of lipopolysaccharide-induced inflammatory response by fragments from serum amyloid A".Journal of Immunology 199.3(2017):1105-1112.
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