SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis

Autor: Satoru Nakata, Seiji Hasegawa, Hirohiko Akamatsu, Kazumitsu Sugiura, Ayumi Sanada, Takaaki Yamada, Masaru Arima, Yohei Iwata, Ogata Yuichiro
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Gene Expression
Apoptosis
Matrix metalloproteinase
Biochemistry
030207 dermatology & venereal diseases
0302 clinical medicine
Macrophage
Chemistry
Cell Polarity
Dermis
Immunohistochemistry
Cell biology
medicine.anatomical_structure
Tumor necrosis factor alpha
Female
Adult
Receptors
CCR7
Cell Survival
Phagocytosis
Cell Adhesion Molecules
Neuronal
Receptors
Lymphocyte Homing
Antigens
Differentiation
Myelomonocytic
Receptors
Cell Surface
Dermatology
Proinflammatory cytokine
Cell Line
03 medical and health sciences
Young Adult
Antigens
CD
medicine
Humans
S100 Calcium-Binding Protein A4
Fibroblast
Molecular Biology
Cyclin-Dependent Kinase Inhibitor p16
Aged
Macrophages
Fibroblasts
Coculture Techniques
Infliximab
030104 developmental biology
Culture Media
Conditioned
RNA
Tumor Necrosis Factor Inhibitors
Senescence-Associated Secretory Phenotype
Zdroj: Experimental dermatologyREFERENCES. 30(1)
ISSN: 1600-0625
Popis: Recently, increasing attention has been paid to senescence-associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co-culture experiments of senescent fibroblasts and macrophages revealed a two-step clearance mechanism: first, TNF-α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage-dependent clearance functions and thereby cause further accumulation of senescent cells.
Databáze: OpenAIRE
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