IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages

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IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. / Raucci, Federica; Saviano, Anella; Casillo, Gian Marco; Guerra-Rodriguez, Miguel; Mansour, Adel Abo; Piccolo, Marialuisa; Ferraro, Maria Grazia; Panza, Elisabetta; Vellecco, Valentina; Irace, Carlo; Caso, Francesco; Scarpa, Raffaele; Mascolo, Nicola; Alfaifi, Mohammed; Iqbal, Asif Jilani; Maione, Francesco.

In: British Journal of Pharmacology, 17.02.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Raucci, F, Saviano, A, Casillo, GM, Guerra-Rodriguez, M, Mansour, AA, Piccolo, M, Ferraro, MG, Panza, E, Vellecco, V, Irace, C, Caso, F, Scarpa, R, Mascolo, N, Alfaifi, M, Iqbal, AJ & Maione, F 2021, 'IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages', British Journal of Pharmacology. https://doi.org/10.1111/bph.15413

APA

Raucci, F., Saviano, A., Casillo, G. M., Guerra-Rodriguez, M., Mansour, A. A., Piccolo, M., Ferraro, M. G., Panza, E., Vellecco, V., Irace, C., Caso, F., Scarpa, R., Mascolo, N., Alfaifi, M., Iqbal, A. J., & Maione, F. (2021). IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. British Journal of Pharmacology. https://doi.org/10.1111/bph.15413

Vancouver

Author

Raucci, Federica ; Saviano, Anella ; Casillo, Gian Marco ; Guerra-Rodriguez, Miguel ; Mansour, Adel Abo ; Piccolo, Marialuisa ; Ferraro, Maria Grazia ; Panza, Elisabetta ; Vellecco, Valentina ; Irace, Carlo ; Caso, Francesco ; Scarpa, Raffaele ; Mascolo, Nicola ; Alfaifi, Mohammed ; Iqbal, Asif Jilani ; Maione, Francesco. / IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. In: British Journal of Pharmacology. 2021.

Bibtex

@article{e90f35e3881648b58691cbcc1286d930,
title = "IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages",
abstract = "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. ",
keywords = "IL-17A, PGE, PPAR-γ, inflammation, mPGES-1, monocytes/macrophages",
author = "Federica Raucci and Anella Saviano and Casillo, {Gian Marco} and Miguel Guerra-Rodriguez and Mansour, {Adel Abo} and Marialuisa Piccolo and Ferraro, {Maria Grazia} and Elisabetta Panza and Valentina Vellecco and Carlo Irace and Francesco Caso and Raffaele Scarpa and Nicola Mascolo and Mohammed Alfaifi and Iqbal, {Asif Jilani} and Francesco Maione",
note = "Funding Information: This work was supported by MIUR (PRIN 2017; 2017A95NCJ/201795NCJ_002, “Stolen molecules ‐ Stealing natural products from the depot and reselling them as new drug candidates”) and Birmingham Fellowship awarded to A.J.I. Publisher Copyright: {\textcopyright} 2021 The British Pharmacological Society",
year = "2021",
month = feb,
day = "17",
doi = "10.1111/bph.15413",
language = "English",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages

AU - Raucci, Federica

AU - Saviano, Anella

AU - Casillo, Gian Marco

AU - Guerra-Rodriguez, Miguel

AU - Mansour, Adel Abo

AU - Piccolo, Marialuisa

AU - Ferraro, Maria Grazia

AU - Panza, Elisabetta

AU - Vellecco, Valentina

AU - Irace, Carlo

AU - Caso, Francesco

AU - Scarpa, Raffaele

AU - Mascolo, Nicola

AU - Alfaifi, Mohammed

AU - Iqbal, Asif Jilani

AU - Maione, Francesco

N1 - Funding Information: This work was supported by MIUR (PRIN 2017; 2017A95NCJ/201795NCJ_002, “Stolen molecules ‐ Stealing natural products from the depot and reselling them as new drug candidates”) and Birmingham Fellowship awarded to A.J.I. Publisher Copyright: © 2021 The British Pharmacological Society

PY - 2021/2/17

Y1 - 2021/2/17

N2 - 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.

AB - 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.

KW - IL-17A

KW - PGE

KW - PPAR-γ

KW - inflammation

KW - mPGES-1

KW - monocytes/macrophages

UR - http://www.scopus.com/inward/record.url?scp=85102740363&partnerID=8YFLogxK

U2 - 10.1111/bph.15413

DO - 10.1111/bph.15413

M3 - Article

C2 - 33595097

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

ER -