Abstract: SA-PO624
Lipoxins Promote Tissue Repair And Regeneration
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Andrews, Darrell C., University College Dublin, Dublin, Ireland
- de Gaetano, Monica, University College Dublin, Dublin, Ireland
- Brennan, Eoin P., University College Dublin, Dublin, Ireland
- Godson, Catherine, The Conway Institute of Biomolecular and Biomedical, Belfield, Dublin, Wilton, Ireland
Background
Inflammation and its timely resolution is essential in maintaining tissue homeostasis during injury and infection. Chronic low-grade inflammation contributes to the pathogenesis of CKD and failure to resolve this leads to impaired tissue repair. Conventional therapeutics such as steroids and non–steroidal anti-inflammatory drugs target the key drivers of the inflammation to dampen the inflammatory response but fail promote inflammation resolution or tissue repair. The resolution phase of inflammation is dynamically regulated by endogenously generated mediators including bioactive lipids such as lipoxins and deficits in these mediator networks may underlie chronic inflammation. We have previously demonstrated reno-protection by lipoxins in experimental models of acute and chronic renal injury (Brennan et al, JASN 2018). Now we wish to explore the therapeutic potential of lipoxins to promote tissue repair and regeneration.
Methods
To investigate the potential of lipoxins to promote tissue repair and regeneration the median tail fin of wild-type 3dpf zebrafish larvae was transected. 4 hours post-injury larvae were treated with LXA4 or vehicle and tissue regeneration tracked by time lapse imaging over 48 hours. The effect of lipoxins on the activation and recruitment of PMNs during tail fin injury was monitored using fluorescent imaging in the transgenic zebrafish lines Tg(mpx:EGFP) and Tg(MPEG1:mCherry). The effect of lipoxins on macrophage subsets was further investigated in human THP-1 derived macrophages treated with TNFα.
Results
Treatment with LXA4 significantly enhanced tail fin regeneration and promoted the resolution of inflammation in the zebrafish model. Furthermore, in THP-1 derived macrophages LXA4 treatment significantly reduced TNF induced inflammation, reprogramming macrophages towards a pro-resolution phenotype as evidenced by up-regulation of IL-4 and MRC1.
Conclusion
These findings suggest that lipoxins promote tissue repair and regeneration by reprogramming macrophages towards a pro-resolution phenotype and may have therapeutic potential for the treatment of chronic inflammation associated with diseases such as CKD.