Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers

Pukstad, Brita S., Ryan, Liv, Flo, Trude H., Stenvik, Jørgen, Moseley, Ryan ORCID: https://orcid.org/0000-0002-2812-6735, Harding, Keith Gordon, Thomas, David William ORCID: https://orcid.org/0000-0001-7319-5820 and Espevik, T. 2010. Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers. Journal of Dermatological Science 59 (2) , pp. 115-122. 10.1016/j.jdermsci.2010.05.003

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Abstract

Background: The molecular pathogenesis of chronic skin wounds is complex and not fully understood. Although these wounds are often characterized as being in a state of persistent inflammation, the impact and participation of the innate immune responses in sustaining this inflammation needs further investigation. Objective: We investigated the cytokine profiles, Toll-like receptor (TLR)-stimulating activities and the levels of the antibacterial peptide Lipocalin-2 (Lcn-2) in a series of healing and non-healing chronic venous leg ulcers (CVLUs) through a study time of 8 weeks. Methods: Wound fluids from healing and non-healing CVLUs were run on a Human Cytokine Antibody Array, and Lcn-2 levels measured with ELISA. HEK 293 cells transfected with TLR2 or TLR4 and their respective co-receptors, and human peripheral blood monocytes were then stimulated with the wound fluids from healing and non-healing venous leg ulcers. Results: Healing wounds were associated with decreasing levels of IL-1 alpha, IL-1 beta and MIP-1 delta, whereas in non-healing wounds decreasing levels of IL-8 and MIP-1 alpha were found. Accordingly, wound fluid from non-healing CVLUs contained persistent Lcn-2 levels and TLR2- and TLR4-stimulating activities, while, in healing wounds, the TLR-stimulating activities decreased over time with significantly diminished levels of Lcn-2 (p < 0.005). Conclusions: Innate immune responses contribute to the chronic inflammation in non-healing CVLUs through participation of Toll-like receptors. The levels of the antimicrobial peptide Lcn-2 in wound fluids from these ulcers are elevated as a reflection of this contribution. (C). 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology R Medicine > RL Dermatology R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Chronic venous leg ulcer (CVLU); Toll-like receptor (TLR); Wound fluid; Lipocalin-2 (Lcn-2)
Publisher:	Elsevier
ISSN:	0923-1811
Last Modified:	18 Oct 2022 13:58
URI:	https://orca.cardiff.ac.uk/id/eprint/16032

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