Identification of a novel negative role of flagellin in regulating IL-10 production |
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Authors: | Vicente-Suarez Ildefonso Takahashi Yoshinori Cheng Fengdong Horna Pedro Wang Hong W Wang Hong-Gang Sotomayor Eduardo M |
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Affiliation: | Division of Immunology, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, FL 33612, USA. |
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Abstract: | Toll-like receptors (TLR) expressed by cells of the immune system play a central role in the generation of immune responses against pathogens. Following TLR ligation, both pro-inflammatory and anti-inflammatory mediators are produced in order to elicit an immune response that controls the microbial infection while limiting tissue damage. Among these mediators, the pro-inflammatory cytokine IL-12 and the anti-inflammatory cytokine IL-10 are known to play major roles. Here, we show that in vitro or in vivo stimulation with flagellin, the TLR5 ligand, does not result in IL-10 production. Furthermore, flagellin inhibits IL-10 production by other specific TLR ligands at the protein and mRNA levels while increasing IL-12p70 production. Several studies have linked the activation of extracellular signal-regulated kinases with IL-10 induction by TLR. We have observed that LPS-induced extracellular signal-regulated kinase activation was significantly decreased in flagellin-treated macrophages, suggesting that this pathway might play a role in the inhibition of IL-10 production observed in flagellin-treated macrophages. Flagellin-mediated IL-10 inhibition was not observed in cells that do not express TLR5, supporting that this effect is indeed TLR5-dependent. This study provides a new insight into the role of flagellin recognition by TLR5 in shaping the immune response elicited by flagellated microorganisms. |
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Keywords: | Flagellin Macrophages TLR5 Toll‐like receptors |
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