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Title: Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)

Abstract

Highlights: {yields} We focused on the interaction between SR-A and TLR4 signaling in this study. {yields} SR-A deletion promoted NF{kappa}B activation in macrophages in septic model mouse. {yields} SR-A suppresses both MyD88-dependent and -independent TLR4 signaling in vitro. {yields} SR-A clears LPS binding to TLR4 which resulting in the suppression of TLR4 signals. -- Abstract: The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A{sup -/-}) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and interferon (IFN)-{beta} were significantly increased in SR-A{sup -/-} mice compared to wild-type mice, and elevated nuclear factor kappa B (NF{kappa}B) activation was detected in SR-A{sup -/-} macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NF{kappa}B in vitro. SR-A deletion also promoted the nuclear translocation of NF{kappa}B and IFN regulatory factor (IRF)-3. Inmore » addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A{sup -/-} macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.« less

Authors:
; ; ;  [1];  [1];  [1];  [1];  [1]
  1. Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)
Publication Date:
OSTI Identifier:
22207426
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 411; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIBODIES; BLOOD; IN VITRO; INFLAMMATION; INTERFERON; LIGANDS; LIPOPROTEINS; MACROPHAGES; MICE; PHOSPHORYLATION; RECEPTORS; TRANSLOCATION

Citation Formats

Ohnishi, Koji, Komohara, Yoshihiro, Fujiwara, Yukio, Takemura, Kenichi, Lei, XiaoFeng, Department of Biochemistry, Showa University School of Medicine, Tokyo, Nakagawa, Takenobu, Sakashita, Naomi, Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima, and Takeya, Motohiro. Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.06.161.
Ohnishi, Koji, Komohara, Yoshihiro, Fujiwara, Yukio, Takemura, Kenichi, Lei, XiaoFeng, Department of Biochemistry, Showa University School of Medicine, Tokyo, Nakagawa, Takenobu, Sakashita, Naomi, Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima, & Takeya, Motohiro. Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). United States. https://doi.org/10.1016/J.BBRC.2011.06.161
Ohnishi, Koji, Komohara, Yoshihiro, Fujiwara, Yukio, Takemura, Kenichi, Lei, XiaoFeng, Department of Biochemistry, Showa University School of Medicine, Tokyo, Nakagawa, Takenobu, Sakashita, Naomi, Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima, and Takeya, Motohiro. 2011. "Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)". United States. https://doi.org/10.1016/J.BBRC.2011.06.161.
@article{osti_22207426,
title = {Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)},
author = {Ohnishi, Koji and Komohara, Yoshihiro and Fujiwara, Yukio and Takemura, Kenichi and Lei, XiaoFeng and Department of Biochemistry, Showa University School of Medicine, Tokyo and Nakagawa, Takenobu and Sakashita, Naomi and Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima and Takeya, Motohiro},
abstractNote = {Highlights: {yields} We focused on the interaction between SR-A and TLR4 signaling in this study. {yields} SR-A deletion promoted NF{kappa}B activation in macrophages in septic model mouse. {yields} SR-A suppresses both MyD88-dependent and -independent TLR4 signaling in vitro. {yields} SR-A clears LPS binding to TLR4 which resulting in the suppression of TLR4 signals. -- Abstract: The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A{sup -/-}) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and interferon (IFN)-{beta} were significantly increased in SR-A{sup -/-} mice compared to wild-type mice, and elevated nuclear factor kappa B (NF{kappa}B) activation was detected in SR-A{sup -/-} macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NF{kappa}B in vitro. SR-A deletion also promoted the nuclear translocation of NF{kappa}B and IFN regulatory factor (IRF)-3. In addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A{sup -/-} macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.},
doi = {10.1016/J.BBRC.2011.06.161},
url = {https://www.osti.gov/biblio/22207426}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 411,
place = {United States},
year = {Fri Aug 05 00:00:00 EDT 2011},
month = {Fri Aug 05 00:00:00 EDT 2011}
}