IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages.
Br J Pharmacol
; 179(9): 1857-1873, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-33595097
ABSTRACT
BACKGROUND AND PURPOSE:
Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal PGE2 synthase (mPGES) and PPAR-γ expression are modulated by a variety of inflammatory factors and stimuli. Considering that very little is known about the biological effects promoted by IL-17 in the context of mPGES-1/PPAR-γ modulation, we sought to investigate the contribution of this unique cytokine on this integrated pathway during the onset of inflammation. EXPERIMENTALAPPROACH:
We evaluated effects of PF 9184 (mPGES-1 inhibitor) and troglitazone (PPAR-γ agonist) in vitro, using the mouse macrophage cell line J774A.1. In vivo, the dorsal air pouch model in CD1 mice was used, and inflammatory infiltrates were analysed by flow cytometry. Locally produced cyto-chemokines and PGs were assessed using elisa assays. Western blots were also employed to determine the activity of various enzymes involved in downstream signalling pathways. KEYRESULTS:
PF 9184 and troglitazone, in a time- and dose-dependent manner, modulated leukocyte infiltration, myeloperoxidase activity, and the expression of COX-2/mPGES-1, NF-кB/IкB-α, and mPTGDS-1/PPAR-γ, induced by IL-17. Moreover, both PF 9184 and troglitazone modulated PG (PGE2 , PGD2 , and PGJ2 ) production, the expression of different pro-inflammatory cyto-chemokines, and the recruitment of inflammatory monocytes, in response to IL-17. CONCLUSIONS AND IMPLICATIONS Our data suggest that IL-17 may constitute a specific modulator of inflammatory monocytes during later phases of the inflammatory response. The results of this study show, for the first time, that the IL-17/mPGES-1/PPAR-γ pathway could represent a potential therapeutic target for inflammatory-based and immune-mediated diseases. LINKED ARTICLES This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http//onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-17
/
PPAR gamma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia