Regulation of IL (Interleukin)-33 Production in Endothelial Cells via Kinase Activation and Fas/CD95 Upregulation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Arteriosclerosis, Thrombosis, and Vascular Biology Année : 2020

Regulation of IL (Interleukin)-33 Production in Endothelial Cells via Kinase Activation and Fas/CD95 Upregulation

Résumé

Objective: The occurrence of new blood vessel formation in the lungs of asthmatic patients suggests a critical role for airway endothelial cells (ECs) in the disease. IL-33 (Interleukin-33)—a cytokine abundantly expressed in human lung ECs—recently emerged as a key factor in the development of allergic diseases, including asthma. In the present study, we evaluated whether mouse and human ECs exposed to the common Dermatophagoides farinae allergen produce IL-33 and characterized the activated signaling pathways. Approach and Results: Mouse primary lung ECs were exposed in vitro to D farinae extract or rmIL-33 (recombinant murine IL-33). Both D farinae and rmIL-33 induced Il-33 transcription without increasing the IL-33 production and upregulated the expression of its receptor, as well as genes involved in angiogenesis and the regulation of immune responses. In particular, D farinae and rmIL-33 upregulated Fas/Cd95 transcript level, yet without promoting apoptosis. Inhibition of caspases involved in the Fas signaling pathway, increased IL-33 protein level in ECs, suggesting that Fas may decrease IL-33 level through caspase-8-dependent mechanisms. Our data also showed that the NF-κB (nuclear factor-κB), PI3K/Akt, and Wnt/β-catenin pathways regulate Il-33 transcription in both mouse and human primary ECs. Conclusions: Herein, we described a new mechanism involved in the control of IL-33 production in lung ECs exposed to allergens.

Dates et versions

hal-03041570 , version 1 (05-12-2020)

Identifiants

Citer

Catherine Duez, Barbara Gross, Philippe Marquillies, Valérie Ledroit, Bernhard Ryffel, et al.. Regulation of IL (Interleukin)-33 Production in Endothelial Cells via Kinase Activation and Fas/CD95 Upregulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 2020, 40 (11), pp.2619-2631. ⟨10.1161/ATVBAHA.120.314832⟩. ⟨hal-03041570⟩
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