Vitamin D 3 inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing.

Autor: Sayegh S; Division of Medicine, University College London, London, UK., Fantecelle CH; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil., Laphanuwat P; Division of Medicine, University College London, London, UK., Subramanian P; Division of Medicine, University College London, London, UK., Rustin MHA; Department of Dermatology, Royal Free Hospital, London, UK., Gomes DCO; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil., Akbar AN; Division of Medicine, University College London, London, UK., Chambers ES; Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Apr; Vol. 23 (4), pp. e14093. Date of Electronic Publication: 2024 Jan 29.
DOI: 10.1111/acel.14093
Abstrakt: Vitamin D 3 replacement in older insufficient adults significantly improves their antigen-specific varicella zoster virus (VZV) cutaneous immunity. However, the mechanisms involved in this enhancement of cutaneous immunity are not known. Here, we show for the first time that vitamin D 3 blocks the senescence-associated secretory phenotype (SASP) production by senescent fibroblasts by partially inhibiting the p38 MAPK pathway. Furthermore, transcriptomic analysis of skin biopsies from older subjects after vitamin D 3 supplementation shows that vitamin D 3 inhibits the same inflammatory pathways in response to saline as the specific p38 inhibitor, losmapimod, which also enhances immunity in the skin of older subjects. Vitamin D 3 supplementation therefore may enhance immunity during ageing in part by blocking p38 MAPK signalling and in turn inhibit SASP production from senescent cells in vivo.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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