Therapeutic Potential of Lipoxin A4 in Chronic Inflammation: Focus on Cardiometabolic Disease

Ting Fu; Muthukumar Mohan; Eoin P Brennan; Owen L Woodman; Catherine Godson; Phillip Kantharidis; Rebecca H Ritchie; Cheng Xue Qin

doi:10.1021/acsptsci.9b00097

Therapeutic Potential of Lipoxin A₄ in Chronic Inflammation: Focus on Cardiometabolic Disease

ACS Pharmacol Transl Sci. 2020 Jan 17;3(1):43-55. doi: 10.1021/acsptsci.9b00097. eCollection 2020 Feb 14.

Authors

Ting Fu^{1

2}, Muthukumar Mohan³, Eoin P Brennan⁴, Owen L Woodman¹, Catherine Godson⁴, Phillip Kantharidis³, Rebecca H Ritchie^{3

1

2

5}, Cheng Xue Qin^{1

2

3}

Affiliations

¹ Heart Failure Pharmacology, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
² Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
³ Department of Diabetes, Central Clinical School, Monash University, Clayton, Victoria 3800, Australia.
⁴ UCD Diabetes Complications Research Centre, UCD Conway Institute, UCD School of Medicine, University College Dublin, Dublin, 4, Ireland.
⁵ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

Abstract

Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic inflammatory diseases, including inflammatory bowel disease, diabetic complications, and cardiometabolic disease. Lipoxins [LXs] are a class of endogenously generated mediators that promote the resolution of inflammation. Biological actions of LXs include inhibition of neutrophil infiltration, promotion of macrophage polarization, increase of macrophage efferocytosis, and restoration of tissue homeostasis. Recently, several studies have demonstrated that LXs and synthetic analogues protect tissues from acute and chronic inflammation. The mechanism includes down-regulation of pro-inflammatory cytokines and chemokines (e.g., interleukin-1β and tumor necrosis factor-α), inhibition of the activation of the master pro-inflammatory pathway (e.g., nuclear factor κ-light-chain-enhancer of activated B cells pathway) and increased release of the pro-resolving cytokines (e.g., interleukin-10). Three generations of LXs analogues are well described in the literature, and more recently a fourth generation has been generated that appears to show enhanced potency. In this review, we will briefly discuss the potential therapeutic opportunity provided by lipoxin A₄ as a novel approach to treat chronic inflammatory disorders, focusing on cardiometabolic disease and the current drug development in this area.

Publication types

Review