Oral administration of EPA-rich oil impairs collagen reorganization due to elevated production of IL-10 during skin wound healing in mice

Beatriz Burger,Hosana G Rodrigues,Jéssica R Silva,Thamiris Candreva,Sílvio R Consonni,Marco Aurélio R Vinolo,Philip C Calder,Helena L Fisk,Bianca G Castelucci,Renato Da S Cardoso,Carolina M C Kühl

doi:10.1038/s41598-019-45508-1

Abstract

Wound healing is an essential process for organism survival. Some fatty acids have been described as modulators of wound healing. However, the role of omega-3 fatty acids is unclear. In the present work, we investigate the effects of oral administration of eicosapentaenoic acid (EPA)-rich oil on wound healing in mice. After 4 weeks of EPA-rich oil supplementation (2 g/kg of body weight), mice had increased serum concentrations of EPA (20:5ω-3) (6-fold) and docosahexaenoic acid (DHA; 22:6ω-3) (33%) in relation to control mice. Omega-3 fatty acids were also incorporated into skin in the EPA fed mice. The wound healing process was delayed at the 3rd and 7th days after wounding in mice that received EPA-rich oil when compared to control mice but there was no effect on the total time required for wound closure. Collagen reorganization, that impacts the quality of the wound tissue, was impaired after EPA-rich oil supplementation. These effects were associated with an increase of M2 macrophages (twice in relation to control animals) and interleukin-10 (IL-10) concentrations in tissue in the initial stages of wound healing. In the absence of IL-10 (IL-10−/− mice), wound closure and organization of collagen were normalized even when EPA was fed, supporting that the deleterious effects of EPA-rich oil supplementation were due to the excessive production of IL-10. In conclusion, oral administration of EPA-rich oil impairs the quality of wound healing without affecting the wound closure time likely due to an elevation of the anti-inflammatory cytokine IL-10.

Highlights

Skin is the first line of the body’s immunological defense against physical, chemical or biological aggression from the external environment[1,2]
Polyunsaturated fatty acids (PUFAs) of the ω-3 family have been recognized as important anti-inflammatory agents[16], reducing the risk of cardiovascular disease, cancer, Alzheimer’s disease and having a protective effect in rheumatoid arthritis, asthma, Crohn’s disease and psoriasis[21]
This increase was related with elevation in M2 macrophages www.nature.com/scientificreports and in interleukin-10, a key anti-inflammatory cytokine produced by this cell population

Summary

Introduction

Skin is the first line of the body’s immunological defense against physical, chemical or biological aggression from the external environment[1,2]. Mammalian skin is divided into epidermis that contains keratinocytes, and dermis composed of fibroblasts and extracellular matrix (ECM). The dermis and skin appendages have important roles in the reepithelialization process because they provide nutritional and mechanical support and supply progenitor cells for the restoration of the epidermis after wounding[4]. Skin homeostasis is provided by the epidermis, dermis and ECM through the interaction between keratinocytes, fibroblasts and resident immune cells, such as neutrophils, macrophages and T lymphocytes[5]. The organism needs to repair itself quickly to avoid dehydration, blood loss and the entrance of harmful microorganisms. Topical treatment with fatty acids appears to be useful for maintenance of hydration and elasticity of the skin, preventing the entrance of microorganisms and water loss to the external environment[10]

Methods

Results

Conclusion