CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction
Background/AimsChemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity.MethodsCirculating levels of CCL17 and CCL22 we...
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Frontiers Media S.A.
2023-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1154158/full |
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author | Luisa Hueso Patrice Marques Brenda Morant Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Joaquin Ortega Joaquin Ortega José T. Real José T. Real José T. Real María J Sanz María J Sanz María J Sanz Laura Piqueras Laura Piqueras Laura Piqueras |
author_facet | Luisa Hueso Patrice Marques Brenda Morant Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Joaquin Ortega Joaquin Ortega José T. Real José T. Real José T. Real María J Sanz María J Sanz María J Sanz Laura Piqueras Laura Piqueras Laura Piqueras |
author_sort | Luisa Hueso |
collection | DOAJ |
description | Background/AimsChemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity.MethodsCirculating levels of CCL17 and CCL22 were measured in 60 morbidly obese patients (mean age, 45 ± 1 years; body mass index/BMI, 44 ± 1 kg/m2) who had undergone bariatric bypass surgery, and 20 control subjects. Paired subcutaneous (SCAT) and visceral adipose tissue (VCAT) from patients were analysed to measure expression of CCR4 and its ligands by RT-PCR, western blot and immunohistochemical analysis. The effects of CCR4 neutralization ex vivo on leukocyte-endothelial cells were also evaluated.ResultsCompared with controls, morbidly obese patients presented higher circulating levels of CCL17 (p=0.029) and CCL22 (p<0.001) and this increase was positively correlated with BMI (p=0.013 and p=0.0016), and HOMA-IR Index (p=0.042 and p< 0.001). Upregulation of CCR4, CCL17 and CCL22 expression was detected in VCAT in comparison with SCAT (p<0.05). Using the parallel-plate flow chamber model, blockade of endothelial CCR4 function with the neutralizing antibody anti-CCR4 in morbidly obese patients significantly reduced leucocyte adhesiveness to dysfunctional endothelium, a key event in atherogenesis. Additionally, CCL17 and CCL22 increased activation of the ERK1/2 mitogen-activated protein kinase signalling pathway in human aortic endothelial cells, which was significantly reduced by CCR4 inhibition (p=0.016 and p<0.05).ConclusionBased on these findings, pharmacological modulation of the CCR4 axis could represent a new therapeutic approach to prevent adipose tissue dysfunction in obesity. |
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spelling | doaj.art-a28d7df3a61045b2bf143ad9d9095df42023-04-12T04:44:41ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-04-011410.3389/fendo.2023.11541581154158CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunctionLuisa Hueso0Patrice Marques1Brenda Morant2Herminia Gonzalez-Navarro3Herminia Gonzalez-Navarro4Herminia Gonzalez-Navarro5Joaquin Ortega6Joaquin Ortega7José T. Real8José T. Real9José T. Real10María J Sanz11María J Sanz12María J Sanz13Laura Piqueras14Laura Piqueras15Laura Piqueras16INCLIVA Biomedical Research Institute, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainDepartment of Biochemistry, University of Valencia, Valencia, SpainCIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, SpainSurgery Service, University Clinic Hospital of Valencia, Valencia, SpainDepartment of Surgery, University of Valencia, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainCIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, SpainEndocrinology and Nutrition Service, University Clinic Hospital of Valencia, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainCIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, SpainDepartment of Pharmacology, University of Valencia, Valencia, SpainINCLIVA Biomedical Research Institute, Valencia, SpainCIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, SpainDepartment of Pharmacology, University of Valencia, Valencia, SpainBackground/AimsChemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity.MethodsCirculating levels of CCL17 and CCL22 were measured in 60 morbidly obese patients (mean age, 45 ± 1 years; body mass index/BMI, 44 ± 1 kg/m2) who had undergone bariatric bypass surgery, and 20 control subjects. Paired subcutaneous (SCAT) and visceral adipose tissue (VCAT) from patients were analysed to measure expression of CCR4 and its ligands by RT-PCR, western blot and immunohistochemical analysis. The effects of CCR4 neutralization ex vivo on leukocyte-endothelial cells were also evaluated.ResultsCompared with controls, morbidly obese patients presented higher circulating levels of CCL17 (p=0.029) and CCL22 (p<0.001) and this increase was positively correlated with BMI (p=0.013 and p=0.0016), and HOMA-IR Index (p=0.042 and p< 0.001). Upregulation of CCR4, CCL17 and CCL22 expression was detected in VCAT in comparison with SCAT (p<0.05). Using the parallel-plate flow chamber model, blockade of endothelial CCR4 function with the neutralizing antibody anti-CCR4 in morbidly obese patients significantly reduced leucocyte adhesiveness to dysfunctional endothelium, a key event in atherogenesis. Additionally, CCL17 and CCL22 increased activation of the ERK1/2 mitogen-activated protein kinase signalling pathway in human aortic endothelial cells, which was significantly reduced by CCR4 inhibition (p=0.016 and p<0.05).ConclusionBased on these findings, pharmacological modulation of the CCR4 axis could represent a new therapeutic approach to prevent adipose tissue dysfunction in obesity.https://www.frontiersin.org/articles/10.3389/fendo.2023.1154158/fullobesityadipose tissuechemokinesinflammationendotheliumCCL22 |
spellingShingle | Luisa Hueso Patrice Marques Brenda Morant Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Herminia Gonzalez-Navarro Joaquin Ortega Joaquin Ortega José T. Real José T. Real José T. Real María J Sanz María J Sanz María J Sanz Laura Piqueras Laura Piqueras Laura Piqueras CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction Frontiers in Endocrinology obesity adipose tissue chemokines inflammation endothelium CCL22 |
title | CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
title_full | CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
title_fullStr | CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
title_full_unstemmed | CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
title_short | CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
title_sort | ccl17 and ccl22 chemokines are upregulated in human obesity and play a role in vascular dysfunction |
topic | obesity adipose tissue chemokines inflammation endothelium CCL22 |
url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1154158/full |
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