Docosahexaenoic acid slows inflammation resolution and impairs the quality of healed skin tissue

Author(s):Show less -

Candreva, Thamiris ^[1] ; Kuhl, Carolina M. C. ^[1] ; Burger, Beatriz ^[1] ; dos Anjos, Mariah B. P. ^[1] ; Torsoni, Marcio A. ^[2] ; Consonni, Silvio R. ^[3] ; Crisma, Amanda R. ^[4] ; Fisk, Helena L. ^[5] ; Calder, Philip C. ^{[6, 7, 5]} ; de Mato, Felipe C. P. ^[8] ; Sernaglia, Erica M. ^[8] ; Vinolo, Marco A. R. ^[8] ; Rodrigues, Hosana G. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Sch Appl Sci, Lab Nutrients & Tissue Repair, Limeira, SP - Brazil

^[2] Univ Estadual Campinas, Sch Appl Sci, Lab Metab Disorders, Limeira, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[4] Univ Sao Paulo, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[5] Univ Southampton, Human Dev & Hlth, Fac Med, Southampton, Hants - England

^[6] Univ Southampton, Southampton, Hants - England

^[7] Univ Hosp Southampton NHS Fdn Trust, NIHR Southampton Biomed Res Ctr, Southampton, Hants - England

^[8] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

• Document type: Journal article
• Source: Clinical Science; v. 133, n. 22, p. 2345-2360, NOV 2019.
• Web of Science Citations: 0

Abstract

There is no consensus on the effects of omega-3 (omega-3) fatty acids (FA) on cutaneous repair. To solve this problem, we used 2 different approaches: (1) FAT-1 transgenic mice, capable of producing endogenous omega-3 FA; (2) wild-type (WT) mice orally supplemented with DHA-enriched fish oil. FAT-1 mice had higher systemic (serum) and local (skin tissue) omega-3 FA levels, mainly docosahexaenoic acid (DHA), in comparison with WT mice. FAT-1 mice had increased myeloperoxidase (MPO) activity and content of CXCL-1 and CXCL-2, and reduced IL-10 in the skin wound tissue three days after the wound induction. Inflammation was maintained by an elevated TNF-alpha concentration and presence of inflammatory cells and edema. Neutrophils and macrophages, isolated from FAT-1 mice, also produced increased TNF-alpha and reduced IL-10 levels. In these mice, the wound closure was delayed, with a wound area 6-fold bigger in relation with WT group, on the last day of analysis (14 days post-wounding). This was associated with poor orientation of collagen fibers and structural aspects in repaired tissue. Similarly, DHA group had a delay during late inflammatory phase. This group had increased TNF-alpha content and CD45(+)F4/80(+) cells at the third day after skin wounding and increased concentrations of important metabolites derived from omega-3, like 18-HEPE, and reduced concentrations of those from omega-6 FA. In conclusion, elevated DHA content, achieved in both FAT-1 and DHA groups, slowed inflammation resolution and impaired the quality of healed skin tissue. (AU)

• FAPESP's process: 14/15127-9 - Multiuser equipment approved in grant 2013/06810-4: flow citometry BD Accury
• Grantee: Hosana Gomes Rodrigues
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/06810-4 - Mechanisms of action of omega-3 and omega-6 in the tissue repair process: neuro-immune focus
• Grantee: Hosana Gomes Rodrigues
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/02021-3 - Wound healing in FAT -1 mice: involvement of anti- inflammatory cholinergic pathway
• Grantee: Thamiris Candreva Robles
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/23298-3 - Analysis of phosphatidylcholine lipid fraction in fat-1 animals in the context of wound healing
• Grantee: Thamiris Candreva Robles
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree