Deferiprone has anti-inflammatory properties and reduces fibroblast migration in vitro

Mahnaz Ramezanpour,Alkis J Psaltis,Jason L P Smith,Sarah Vreugde,P J Wormald,Michael Gouzos,Mian Li Ooi

doi:10.1038/s41598-019-38902-2

Mahnaz Ramezanpour, Alkis J Psaltis + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-38902-2

Copy DOI

Abstract

Normal wound healing is a highly regulated and coordinated process. However, tissue injury often results in inflammation with excessive scar tissue formation after 40–70% of operations. Here, we evaluated the effect of the iron chelator deferiprone on inflammation and the migration of primary nasal fibroblasts and primary human nasal epithelial cells (HNECs) in vitro. The cytotoxicity of deferiprone was examined by the lactate dehydrogenase assay on primary nasal fibroblasts and air-liquid interface (ALI) cultures of HNECs. Wound closure was observed in scratch assays by using time-lapse confocal scanning laser microscopy. Interleukin-6 (IL-6) and type I and III collagen protein levels were determined by ELISA. Intracellular Reactive Oxygen Species (ROS) activity was measured by utilizing the fluorescent probe H2DCFDA. Deferiprone at 10 mM concentration was non-toxic to primary fibroblasts and HNECs for up to 48 hours application. Deferiprone had significant dose-dependent inhibitory effects on the migration, secreted collagen production and ROS release by primary nasal fibroblasts. Deferiprone blocked Poly (I:C)-induced IL-6 production by HNECs but did not alter their migration in scratch assays. Deferiprone has the potential to limit scar tissue formation and should be considered in future clinical applications.

Highlights

Scar tissue formation is part of the natural healing process after injury
Deferiprone inhibited reactive oxygen species (ROS) release in human nasal epithelial cells and human sinonasal fibroblasts compared with untreated samples
It has been demonstrated that the critical time interval to block adhesions is primarily in the first few days after the initial injury and that the extent of adhesion formation is largely dependent on the level of inflammation, ROS production, collagen production and fibroblast migration during that time[10,33]

Summary

Introduction

Scar tissue formation is part of the natural healing process after injury. Tissue repair begins within the first few days of an injury and a variety of cytokines and growth factors are involved in the wound healing processes[1]. Whilst low level inflammation is key to normal wound healing, the formation of adhesions or hypertrophic scars following injury can be exacerbated by pathological processes resulting in excessive inflammation[10] These processes include infection and hematoma formation and it has been shown that recruitment of neutrophils and macrophages, producing inflammatory cytokines and reactive oxygen species (ROS) followed by fibroblast migration and proliferation into the wound are critical factors in these processes[3,11,12]. The goal was to determine the effect of deferiprone on fibroblast and epithelial cell migration, collagen production, ROS activity and potential for anti-inflammatory effects to evaluate its potential to limit hypertrophic scar tissue formation for future clinical applications

Methods

Results

Conclusion