G-protein-coupled receptor 84 regulates acute inflammation in normal and diabetic skin wounds

Paula O. Cooper, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Sarah S. Kleb, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Satish K. Noonepalle, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Veronica M. Amuso, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Rohan Varshney, Department of Biochemistry and Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Michael C. Rudolph, Department of Biochemistry and Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Tanvir K. Dhaliwal, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Darlene V. Nguyen, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Miguel F. Mazumder, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Najuma S. Babirye, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Ruchi Gupta, Department of Surgery, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Bao-Ngoc Nguyen, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA; Department of Surgery, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
Brett A. Shook, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA; Department of Dermatology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA. Electronic address: brettshook@gwu.edu.

Document Type

Journal Article

Publication Date

5-29-2024

Journal

Cell reports

Volume

43

Issue

6

DOI

10.1016/j.celrep.2024.114288

Keywords

CP: Metabolism; GPR84; diabetes; inflammation; macrophage; medium-chain fatty acid; wound healing

Abstract

Lipids have emerged as potent regulators of immune cell function. In the skin, adipocyte lipolysis increases the local pool of free fatty acids and is essential for coordinating early macrophage inflammation following injury. Here, we investigate G-protein-coupled receptor 84 (GPR84), a medium-chain fatty acid (MCFA) receptor, for its potential to propagate pro-inflammatory signaling after skin injury. GPR84 signaling was identified as a key component of regulating myeloid cell numbers and subsequent tissue repair through in vivo administration of a pharmacological antagonist and the MCFA decanoic acid. We found that impaired injury-induced dermal adipocyte lipolysis is a hallmark of diabetes, and lipidomic analysis demonstrated that MCFAs are significantly reduced in diabetic murine wounds. Furthermore, local administration of decanoic acid rescued myeloid cell numbers and tissue repair during diabetic wound healing. Thus, GPR84 is a readily targetable lipid signaling pathway for manipulating injury-induced tissue inflammation with beneficial effects on acute diabetic healing.

Department

Biochemistry and Molecular Medicine

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