IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- King Khalid University
- University of Naples Federico II
Background and Purpose: Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal PGE 2 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.
Experimental Approach: 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.
Key Results: 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 (PGE 2, PGD 2, and PGJ 2) 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.
|Journal||British Journal of Pharmacology|
|Early online date||17 Feb 2021|
|Publication status||E-pub ahead of print - 17 Feb 2021|
- IL-17A, PGE, PPAR-γ, inflammation, mPGES-1, monocytes/macrophages