Indication of Activated Senescence Pathways in the Temporal Arteries of Patients With Giant Cell Arteritis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
10
03
2023
received:
10
03
2023
accepted:
10
04
2023
medline:
29
9
2023
pubmed:
15
4
2023
entrez:
14
4
2023
Statut:
ppublish
Résumé
Giant cell arteritis (GCA) affects almost exclusively individuals above 50 years old, suggesting a role of aging-related changes such as cellular senescence in its pathobiology. The kinases p21(WAF1/CIP1) and p16/INK4A play key roles in 2 distinct pathways leading to senescence. The proinflammatory molecules interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are key components of the senescence-associated secretory phenotype (SASP), are effective targets of treatment in GCA. Here, we aimed to investigate the presence of p21+ and p16+ cells producing these SASP cytokines in temporal artery biopsies (TABs) of patients with GCA. Eight patients with GCA and 14 age-matched, non-GCA individuals who underwent a TAB were included. Immunohistochemical staining of p21, p16, IL-6, and GM-CSF was performed. Multiplex immunofluorescent staining was performed to investigate the colocalization of p21 and p16 with IL-6, GM-CSF, and immune cell markers (CD68, CD3, CD20). We found that expression levels of p16, p21, IL-6, and GM-CSF were elevated in the TABs of patients with GCA. Both p16- and p21-expressing cells were mainly found near the internal lamina elastica, especially among giant cells and macrophages, although p21 and p16 expression could be found in all 3 layers of the vessels. Expression of p16 and p21 was occasionally found in T cells but not B cells. The p16+ and p21+ cells expressing GM-CSF/IL-6 were detected throughout the TABs. Our data suggest the presence of activated senescence pathways at the site of vascular inflammation in GCA and support further research into the role of senescence in the pathophysiology of GCA.
Substances chimiques
Biomarkers
0
Cyclin-Dependent Kinase Inhibitor p16
0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Interleukin-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1812-1818Informations de copyright
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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