1. Bacterial Lipoproteins Constitute the TLR2-Stimulating Activity of Serum Amyloid A.
- Author
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Burgess EJ, Hoyt LR, Randall MJ, Mank MM, Bivona JJ 3rd, Eisenhauer PL, Botten JW, Ballif BA, Lam YW, Wargo MJ, Boyson JE, Ather JL, and Poynter ME
- Subjects
- Adult, Animals, Cell Differentiation, Cytokines metabolism, Escherichia coli genetics, Escherichia coli Proteins immunology, HEK293 Cells, Humans, Inflammation Mediators metabolism, Lipoproteins immunology, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Recombinant Proteins genetics, Serum Amyloid A Protein genetics, Leukocytes, Mononuclear immunology, Serum Amyloid A Protein immunology, Th17 Cells immunology, Toll-Like Receptor 2 agonists
- Abstract
Studies comparing endogenous and recombinant serum amyloid A (SAA) have generated conflicting data on the proinflammatory function of these proteins. In exploring this discrepancy, we found that in contrast to commercially sourced recombinant human SAA1 (hSAA1) proteins produced in Escherichia coli , hSAA1 produced from eukaryotic cells did not promote proinflammatory cytokine production from human or mouse cells, induce Th17 differentiation, or stimulate TLR2. Proteomic analysis of E. coli -derived hSAA1 revealed the presence of numerous bacterial proteins, with several being reported or probable lipoproteins. Treatment of hSAA1 with lipoprotein lipase or addition of a lipopeptide to eukaryotic cell-derived hSAA1 inhibited or induced the production of TNF-α from macrophages, respectively. Our results suggest that a function of SAA is in the binding of TLR2-stimulating bacterial proteins, including lipoproteins, and demand that future studies of SAA employ a recombinant protein derived from eukaryotic cells., (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Published
- 2018
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