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IL-17 induced inflammation modulates mPGES-1/PPAR-γ pathways in monocytes/macrophages
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  • Federica Raucci,
  • Anella Saviano,
  • Gian Casillo,
  • Miguel Guerra-Rodriguez,
  • Adel Mansour,
  • Marialuisa Piccolo,
  • Maria Ferraro,
  • Elisabetta Panza,
  • Valentina Vellecco,
  • Carlo Irace,
  • Francesco Caso,
  • Raffaele Scarpa,
  • Nicola Mascolo,
  • Mohammed Alfaifi,
  • Asif Iqbal,
  • Francesco Maione
Federica Raucci
University of Naples Federico II School of Medicine and Surgery
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Anella Saviano
University of Naples Federico II School of Medicine and Surgery
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Gian Casillo
University of Naples Federico II School of Medicine and Surgery
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Miguel Guerra-Rodriguez
University of Birmingham College of Medical and Dental Sciences
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Adel Mansour
University of Birmingham College of Medical and Dental Sciences
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Marialuisa Piccolo
University of Naples Federico II School of Medicine and Surgery
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Maria Ferraro
University of Naples Federico II School of Medicine and Surgery
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Elisabetta Panza
University of Naples Federico II School of Medicine and Surgery
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Valentina Vellecco
University of Naples Federico II School of Medicine and Surgery
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Carlo Irace
University of Naples Federico II School of Medicine and Surgery
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Francesco Caso
University of Naples Federico II School of Medicine and Surgery
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Raffaele Scarpa
University of Naples Federico II School of Medicine and Surgery
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Nicola Mascolo
University of Naples Federico II School of Medicine and Surgery
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Mohammed Alfaifi
King Khalid University
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Asif Iqbal
University of Birmingham College of Medical and Dental Sciences
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Francesco Maione
University of Naples Federico II School of Medicine and Surgery
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Abstract

Background and Purpose: Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal prostaglandin E2 synthase (mPGES) and peroxisome proliferator-activated receptor-γ (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 these integrated pathways during the onset of inflammation. Experimental Approach: We evaluated PF 9184 (mPGES-1 antagonist) and Troglitazone (PPAR-γ agonist) activity utilising integrated in vitro and in vivo approaches. The dorsal air pouch model was employed, and inflammatory infiltrates were analysed by flow cytometry. Locally produced cyto-chemokines and prostaglandins 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, were shown to significantly modulate leukocyte infiltration, myeloperoxidase activity, and the expression of COX-2/mPGES-1, NF-кB/IкB-α and mPGDS-1/PPAR-γ induced by IL-17. Moreover, both compounds were found to modulate prostaglandins (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: Collectively, the data presented suggests that IL-17 may constitute a specific modulator of inflammatory monocytes during later phases of the inflammatory response. Therefore, the results of this study show, for the first time, that IL-17/mPGES-1/PPAR-γ “axis” could represent a potential therapeutic target for inflammatory-based and immune-mediated diseases.

Peer review status:Published

02 Oct 2020Submitted to British Journal of Pharmacology
02 Oct 2020Submission Checks Completed
02 Oct 2020Assigned to Editor
20 Oct 2020Reviewer(s) Assigned
07 Dec 2020Review(s) Completed, Editorial Evaluation Pending
10 Dec 2020Editorial Decision: Revise Minor
14 Jan 20211st Revision Received
17 Jan 2021Submission Checks Completed
17 Jan 2021Assigned to Editor
19 Jan 2021Reviewer(s) Assigned
02 Feb 2021Review(s) Completed, Editorial Evaluation Pending
04 Feb 2021Editorial Decision: Accept
17 Feb 2021Published in British Journal of Pharmacology. 10.1111/bph.15413