Journal
JOURNAL OF DERMATOLOGICAL SCIENCE
Volume 59, Issue 2, Pages 115-122Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2010.05.003
Keywords
Chronic venous leg ulcer (CVLU); Toll-like receptor (TLR); Wound fluid; Lipocalin-2 (Lcn-2)
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Funding
- Norwegian Cancer Society
- Norwegian Research Council
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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.
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