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?(1)-Acid glycoprotein up-regulates CD163 via TLR4/CD14 protein pathway: possible protection against hemolysis-induced oxidative stress.

ABSTRACT: CD163, a scavenger receptor that is expressed at high levels in the monocyte-macrophage system, is a critical factor for the efficient extracellular hemoglobin (Hb) clearance during hemolysis. Because of the enormous detrimental effect of liberated Hb on our body by its ability to induce pro-inflammatory signals and tissue damage, an understanding of the molecular mechanisms associated with CD163 expression during the acute phase response is a central issue. We report here that ?(1)-acid glycoprotein (AGP), an acute phase protein, the serum concentration of which is elevated under various inflammatory conditions, including hemolysis, up-regulates CD163 expression in both macrophage-like differentiated THP-1 (dTHP-1) cells and peripheral blood mononuclear cells in a time- and concentration-dependent manner. Moreover, the subsequent induction of Hb uptake was also observed in AGP-treated dTHP-1 cells. Among representative acute phase proteins such as AGP, ?(1)-antitrypsin, C-reactive protein, and haptoglobin, only AGP increased CD163 expression, suggesting that AGP plays a specific role in the regulation of CD163. Consistently, the physiological concentrations of AGP induced CD163, and the subsequent induction of Hb uptake as well as the reduction of oxidative stress in plasma were observed in phenylhydrazine-induced hemolytic model mice, confirming the in vivo role of AGP. Finally, AGP signaling through the toll-like receptor-4 (TLR4) and CD14, the common innate immune receptor complex that normally recognizes bacterial components, was identified as a crucial stimulus that induces the autocrine regulatory loops of IL-6 and/or IL-10 via NF-?B, p38, and JNK pathways, which leads to an enhancement in CD163 expression. These findings provide possible insights into how AGP exerts anti-inflammatory properties against hemolysis-induced oxidative stress.

SUBMITTER: Komori H

PROVIDER: S-EPMC3436313 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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α(1)-Acid glycoprotein up-regulates CD163 via TLR4/CD14 protein pathway: possible protection against hemolysis-induced oxidative stress.

Komori Hisakazu H Watanabe Hiroshi H Shuto Tsuyoshi T Kodama Azusa A Maeda Hitoshi H Watanabe Kenji K Kai Hirofumi H Otagiri Masaki M Maruyama Toru T

The Journal of biological chemistry 20120717 36

CD163, a scavenger receptor that is expressed at high levels in the monocyte-macrophage system, is a critical factor for the efficient extracellular hemoglobin (Hb) clearance during hemolysis. Because of the enormous detrimental effect of liberated Hb on our body by its ability to induce pro-inflammatory signals and tissue damage, an understanding of the molecular mechanisms associated with CD163 expression during the acute phase response is a central issue. We report here that α(1)-acid glycopr ...[more]

PMID: 22807450

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Project description:ObjectivesThis study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.MethodsIFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.ResultsTwenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).ConclusionsThe quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

Dataset Information

?(1)-Acid glycoprotein up-regulates CD163 via TLR4/CD14 protein pathway: possible protection against hemolysis-induced oxidative stress.

Publications

α(1)-Acid glycoprotein up-regulates CD163 via TLR4/CD14 protein pathway: possible protection against hemolysis-induced oxidative stress.

Similar Datasets

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