Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients

Zhao, Lei; Yamaguchi, Yasushi; Ge, Xiaomei; Robinson, William H.; Morser, John; Leung, Lawrence L.K.

doi:10.1186/s13075-018-1615-y

Cited by 24 publications

(33 citation statements)

References 32 publications

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“…Two of these studies further established a correlation between leptin levels and RA activity [34,35]. Several case-control studies have also suggested associations of chemerin and RBP4 concentrations with RA [36,37]. However, our MR results suggested that genetically predicted levels of adiponectin, leptin, chemerin or RBP4 were not causally associated with risk of RA.…”

Section: Discussionsupporting

confidence: 52%

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

Zhu

Zheng

et al. 2020

Preprint

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Background: Circulating adipokines levels have been reported to be associated with the risk of rheumatoid arthritis (RA). However, it is still unclear whether these associations are causal or biased by reverse causation or residual confounding. This study aimed to assess potential causal roles of five adipokines (namely, adiponectin, leptin, resistin, chemerin, and retinol-blinding protein 4 [RBP4]) in the occurrence of RA.Methods: We conducted a two-sample Mendelian randomization analysis to investigate these associations. We used summary-level data from genome-wide association studies (GWASs) for adipokines in individuals of European ancestry as the exposure, and a separate large-scale meta-analysis of a GWAS which included 14,361 RA cases and 43,923 controls of European ancestry as the outcome. Genetic variants were selected as instrumental variables if robustly genome-wide significant in their associations with adipokines. The causal effects were estimated using the inverse-variance weighted method in the primary analysis. Sensitivity analyses were performed to warrant that bias due to genetic pleiotropy was unlikely.Results: The circulating resistin was found to be the only adipokinetic factor having statistical significance, with higher levels causally associated with the risk of RA (odds ratio: 1.28; 95% confidence interval: [1.07, 1.53] per unit increase in the natural log-transformed resistin). In contrast, associations of adiponectin, leptin, chemerin, and RBP4 with risk of RA were not statistically significant. The MR assumptions did not seem to be violated. Sensitivity analyses yielded consistent findings.Conclusions: Genetically predicted circulating resistin levels were positively associated with RA risk. Our analysis suggested that resistin may play a notable causal role in RA pathogenesis. It would be beneficial for the development of clinical as well as public health strategies that target appropriate levels of resistin for future RA intervention.

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Section: Discussionsupporting

confidence: 52%

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

Zhu

Zheng

et al. 2020

Preprint

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“…The human homologue of mouse mchem155F, hchem156F, on the other hand, is much less potent than hchem157S, while mchem155F is as potent as mchem156S and hchem157S. The possible reasons for hchem156F and mchem155F to display different activities on cells expressing their cognate CMKLR1 are under investigation [ 35 ]. The activity of both mchem162K (mchem161T), the full-length mouse prochemerin form, and mchem157R was modest, analogous to their homologues, human hchem163S and hchem158K.…”

Section: Discussionmentioning

confidence: 99%

Dynamic and tissue-specific proteolytic processing of chemerin in obese mice

et al. 2018

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Chemerin is a chemoattractant involved in immunity as well as an adipokine, whose activity is regulated by successive proteolytic cleavages at its C-terminus. Chemerin’s C-terminal sequence and its proteolytic cleavage sites are highly conserved between human and mouse, as well as in other species. We produced, purified and characterized different mouse chemerin forms. Ca2+ mobilization assay showed that the EC50 values for mchem161T and mchem157R were 135.8 ± 158 nM and 71.2 ± 55.4 nM, respectively, whereas mchem156S and mchem155F had a 20-fold higher potency with an EC50 of 4.6 ± 1.8 nM and 3.6 ± 3.0 nM, respectively, likely representing the two physiologically active forms of chemerin. No agonist activity was found for mchem154A. Similar results were obtained in a chemotaxis assay. To identify and quantify the in vivo mouse chemerin forms in biological samples, we developed specific ELISAs for mchem162K, mchem157R, mchem156S, mchem155F and mchem154A, using antibodies raised against peptides from the C-terminus of the different mouse chemerin forms. The prochemerin form, mchem162K, was the major chemerin form in plasma with its increase matching the increase of total plasma chemerin in obese mice. During the onset of obesity in high-fat diet fed mice, mchem156S was elevated in plasma. In contrast, mchem155F was the dominant form in epididymal fat extracts. Our study provides the first direct evidence that mouse chemerin undergoes extensive, dynamic and tissue-specific proteolytic processing in vivo, similar to human chemerin, underlining the importance of measuring individual chemerin forms in studies of chemerin biology in mouse models.

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“…Rheumatoid arthritis is a long term autoimmune disease manifesting with signs of inflammation, swollen and warm painful joints, in addition to stiffness, particularly early in the morning on waking or following prolonged inactivity [4]. Rheumatoid arthri-Reumatologia 2020; 58/2 tis represents the most common form of autoimmune diseases and immune cell infiltrates are observed in synovial tissues of RA patients [5]. The production of certain inflammatory markers by different cells such as monocytes/macrophages, fibroblast-like synoviocytes, and dendritic cells plays a central role in promoting and maintaining joint inflammation [6].…”

Section: Introductionmentioning

confidence: 99%

Serum chemerin and visfatin levels and their ratio as possible diagnostic parameters of rheumatoid arthritis

Ali¹,

Al-Fadhel²,

Al-Ghuraibawi³

et al. 2020

Reumatologia

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Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovium and articular cartilage that initiates joint damage. Rheumatoid arthritis is associated with a change in many inflammatory biomarkers. The present study aims to examine the diagnostic ability of inflammatory adipocytokines (chemerin and visfatin) and their ratio for RA disease. Material and methods: The study recruited 60 RA patients and 30 healthy controls. Serum visfatin and chemerin were measured using the ELISA technique. Some related parameters including body mass index (BMI), lipid profile components, C-reactive protein (CRP), and uric acid levels were also determined and correlated with the level of these adipokines. Results: Serum chemerin, visfatin, CRP, and uric acid (UA) levels were significantly higher (p < 0.05) in RA patients than those of the control group. The multivariate general linear model (GLM) analysis showed that 70.7% of the change in the level of measured parameters can be explained by the presence of RA disease (partial η 2 = 0.707, p < 0.001). To explore which parameter was affected by the diagnosis, the results of tests between subjects showed that all biomarkers were affected significantly by the diagnosis and the greater effects were on CRP (partial η 2 = 0.480, p < 0.001) followed by chemerin (partial η 2 = 0.295, p < 0.001), while visfatin showed partial η 2 = 0.079 only. Chemerin showed the highest sensitivity (88.1%) and specificity (75.9%) for diagnosis of RA at cutoff concentration = 187.88 ng/ml as compared with other parameters. Conclusions: Chemerin and visfatin levels are affected by RA disease when adjusted for other cofounders. The present results suggest that serum chemerin can be used as an inflammatory marker of RA patients as it has good sensitivity and specificity.

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Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients

Cited by 24 publications

References 32 publications

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

Dynamic and tissue-specific proteolytic processing of chemerin in obese mice

Serum chemerin and visfatin levels and their ratio as possible diagnostic parameters of rheumatoid arthritis

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