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Soluble Receptor for Advanced Glycation End Product Is Involved in the Inflammatory Response of Human Adenovirus-Infected Patients.

ABSTRACT: Human adenovirus (HAdV) infection causes excessive inflammation associated with severe tissue injury, such as pneumonia. The molecules involved in the underlying inflammatory mechanisms remain to be elucidated. Receptor for advanced glycation end product (RAGE) is mainly expressed on immune cells and lung tissues, and it is a key factor in the initiation and development of inflammation. RAGE can be cleaved by metalloprotease 9 (MMP9) to release the extracellular segment, which is named soluble RAGE (sRAGE), into the intercellular space, where it can bind to RAGE ligands and block RAGE activation and subsequent inflammation. In our study, we enrolled HAdV-infected patients and their contacts to examine the relationship between sRAGE and inflammation induced by HAdV infection. The results showed that HAdV infection stimulated inflammatory cytokine secretion, increased such as high mobility group box 1 (HMGB1) levels, and suppressed sRAGE expression. sRAGE levels were significantly different between patients with or without pneumonia. We also found that MMP9 was significantly lower in patients with pneumonia, and it was positively correlated with sRAGE levels over 7 days after disease onset. The mitogen-activated protein kinase (MAPK) pathway is an important immune activation signaling pathway that is regulated by RAGE. We observed the activation of the MAPK pathway in the peripheral blood mononuclear cells (PBMCs) of patients. Negative correlations between sRAGE and phosphorylated JNK and p38 were observed. These results suggest that sRAGE is involved in HAdV-induced inflammatory responses, and might be a potential therapeutic target to alleviate the HAdV-induced excessive inflammation.

SUBMITTER: Xu W

PROVIDER: S-EPMC9301492 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

Project description:ObjectivesPatients with bicuspid aortic valve (BAV) have a high risk of aortic dilation and adverse vascular events. Previous studies had reported soluble receptor for advanced glycation end products (sRAGE) to compete with receptor of advanced glycation end products (RAGE) for ligand binding and inhibit the activation of nuclear-factor kappa-B (NF-κB) pathway and matrix metalloproteinases (MMP) transcription. Thus, sRAGE serum levels may contribute to the clinical diagnosis and monitoring of ascending aorta aneurysm in patients with BAV.MethodsTo eliminate the confounding factors, 44 patients with BAV were divided into 3 subgroups according to the diameter of ascending aorta, and 20 patients with tricuspid aortic valve and normal-sized ascending aorta were selected as a control group. Protein levels and gene transcription of several variates were evaluated in the tissue and serum samples from these patients. Human aortic smooth muscle cells were treated with AGE-BSA in gradient concentrations, and changes in phenotype and protein and mRNA levels were detected.ResultsSerum levels of sRAGE in the 3 BAV groups were obviously higher than those in the tricuspid aortic valve group, although there was negative correlation between the serum sRAGE levels and ascending aortic diameters among patients with BAV. Transcript expression levels of RAGE and NF-κBp65 mRNA were increased in the 3 BAV groups and RAGE/NF-κB pathway was activated with the progression of ascending aortic aneurysm. Abnormal activation of RAGE/NF-κB pathway was observed in AGE-BSA-treated human aortic smooth muscle cells.ConclusionsOur study has shown a trend in serum levels of sRAGE among patients with BAV, and that the cellular and extracellular pathological processes are quite serious even in the normal-sized or slightly dilated aorta. Together, the findings indicated that sRAGE may be used as a biomarker to predict aneurysm expansion rates and the risk of adverse vascular events.

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Soluble Receptor for Advanced Glycation End Product Is Involved in the Inflammatory Response of Human Adenovirus-Infected Patients.

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