Abstract
Follistatin-related protein (FRP)/follistatin-like 1 (FSTL1) has multi-specific binding nature especially with TGF-β superfamily proteins, and thereby modulates organ development. However, its function in immune systems remains unclear. Previously, we reported FRP interacts with CD14, which is known to mediate toll-like receptor 4 (TLR4) signaling. Here, we investigated whether FRP activates TLR4 signaling. Recombinant FRP induced interleukin 6 or interleukin 8 production from target cells in a CD14- and TLR4-dependent manner. Moreover, similar to lipopolysaccharide (LPS), FRP induced tolerance to the second LPS stimulation. FRP has the function of evoking innate immune responses as one of the endogenous TLR4 agonists.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Follistatin-Related Proteins / antagonists & inhibitors
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Follistatin-Related Proteins / genetics
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Follistatin-Related Proteins / immunology*
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Follistatin-Related Proteins / pharmacology
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Gene Knockdown Techniques
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HEK293 Cells
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Humans
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Immunity, Innate*
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Interleukin-6 / biosynthesis
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Interleukin-8 / biosynthesis
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Lipopolysaccharide Receptors / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Knockout
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NIH 3T3 Cells
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Recombinant Proteins / pharmacology
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Signal Transduction
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Toll-Like Receptor 4 / agonists
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Toll-Like Receptor 4 / deficiency
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / metabolism*
Substances
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CXCL8 protein, human
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Follistatin-Related Proteins
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Fstl1 protein, mouse
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IL6 protein, human
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Interleukin-6
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Interleukin-8
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Lipopolysaccharide Receptors
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Recombinant Proteins
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TLR4 protein, human
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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FSTL1 protein, human