Cited by 120Adipokines, Inflammation, and Metabolic DiseasesChemokine receptors and signalingCardiovascular Disease and Adiposity

Roles of Chemokine Ligand-2 (CXCL2) and Neutrophils in Influencing Endothelial Cell Function and Inflammation of Human Adipose Tissue

Rouault, Christine, Pellegrinelli, Vanessa, Schilch, Raphaela, Cotillard, Aurélie, Poitou, Christine, Tordjman, Joan, Sell, Henrike, Clément, Karine +1 more·2013·Endocrinology

Abstract

The hypertrophied white adipose tissue (WAT) during human obesity produces inflammatory mediators, including cytokines (IL-6 and TNFα) and chemokines ([C-C motif] chemokine ligand 2 and IL-8). These inflammatory factors are preferentially produced by the nonadipose cells, particularly the adipose tissue infiltrating macrophages. We identified the chemokine (C-X-C motif) ligand 2 (CXCL2) by a transcriptomic approach. Because CXCL2 could represent a WAT-produced chemokine, we explored its role in obesity-associated inflammation. CXCL2 levels in serum and mRNA in WAT were higher in obese subjects compared with lean ones. CXCL2 secretions were higher in sc and visceral (vis) WAT from obese compared with lean subjects. In vis WAT, CXCL2 mRNA expression was higher in macrophages compared with other WAT cells and positively correlated with the inflammatory macrophage markers TNFα and IL-6. CXCL2 triggered the in vitro adhesion of the neutrophils, its selective cell targets, to endothelial cells (ECs) of vis WAT (vis WAT-ECs). Immunohistological analysis indicated that activated neutrophils were adherent to the endothelium of vis WAT from human obese subjects. Blood neutrophils from obese subjects released high levels of proinflammatory mediators (IL-8, chemokine motif ligand 2 [CCL2], matrix metalloproteinase [MMP] 9, and myeloperoxidase [MPO]). Visceral WAT-ECs, treated by neutrophil-conditioned media prepared from obese subjects, displayed an increase of the expression of inflammatory molecules associated with senescence and angiogenic capacities. To conclude, CXCL2, a WAT-produced chemokine being up-regulated in obesity, stimulates neutrophil adhesion to vis WAT-ECs. Activated neutrophils in obesity may influence vis WAT-ECs functions and contribute to WAT inflammation.

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Crossref · 10.1210/en.2012-1415

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Authors
Rouault, C., Pellegrinelli, V., Schilch, R., Cotillard, A., Poitou, C., Tordjman, J., Sell, H., Clément, K., & Lacasa, D.
Affiliations
  • Inserm (FR)
  • Deutsches Diabetes-Zentrum e.V. (DE)
Corresponding author
Lacasa, Danièle
Venue
Endocrinology
Published
2013-03-01
Volume
154
Issue
3
Pages
1069-1079
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2051659042
Cited by
119
References
44
Citations by year
2026: 4 · 2025: 7 · 2024: 13 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 16 · 2019: 11 · 2018: 6 · 2017: 10 · 2016: 11 · 2015: 6 · 2014: 6 · 2013: 2
FWCI
6.05
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
CXCL2, neutrophils, endothelial cells, white adipose tissue, obesity, adipose tissue inflammation, visceral adipose tissue, subcutaneous adipose tissue, adipose tissue macrophages, neutrophil adhesion, chemokines, interleukin-6, TNF-α, interleukin-8, MMP-9, myeloperoxidase, endothelial cell senescence, angiogenesis
MeSH terms
Adult, Cell Adhesion, Female, Humans, Inflammation, Neutrophils, Obesity, Morbid, RNA, Messenger, Case-Control Studies, Neutrophil Activation, Inflammation Mediators, Chemokines, Endothelial Cells, Adipose Tissue, White, Chemokine CXCL2

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