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

Journal of Dermatological Science

Volumn 59, Issue 2, 2010, Pages 115-122

  Pukstad, Brita S ^a,c   Ryan, Liv ^a   Flo, Trude H ^a   Stenvik, Jørgen ^a   Moseley, Ryan ^b   Harding, Keith ^b   Thomas, David W ^b   Espevik, Terje ^a  

^a NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

Author keywords

Chronic venous leg ulcer (CVLU); Lipocalin 2 (Lcn 2); Toll like receptor (TLR); Wound fluid

Indexed keywords

INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN; MACROPHAGE INFLAMMATORY PROTEIN 1DELTA; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ARTICLE; CELL STRAIN HEK293; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE DURATION; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; HUMAN CELL; IMMUNOPATHOGENESIS; IMMUNOSTIMULATION; INNATE IMMUNITY; LEG ULCER; MONOCYTE; PRIORITY JOURNAL; WOUND FLUID; WOUND HEALING;

ACUTE-PHASE PROTEINS; CELLS, CULTURED; CHEMOKINE CCL3; CHRONIC DISEASE; HUMANS; IMMUNITY, INNATE; INTERLEUKIN-8; KIDNEY; LEUKOCYTES, MONONUCLEAR; LIPOCALINS; PROTO-ONCOGENE PROTEINS; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 4; VARICOSE ULCER; WOUND HEALING;

EID: 77955052631     PISSN: 09231811     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jdermsci.2010.05.003     Document Type: Article

References (61)

1. Margolis D.J., Bilker W., Santanna J., Baumgarten M. Venous leg ulcer: incidence and prevalence in the elderly. J Am Acad Dermatol 2002, 46:381-386.
2. Schultz G.S., Sibbald R.G., Falanga V., Ayello E.A., Dowsett C., Harding K., et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen 2003, 11(Suppl. 1):S1-S28.
3. Moseley R., Stewart J.E., Stephens P., Waddington R.J., Thomas D.W. Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases?. Br J Dermatol 2004, 150:401-413.
4. Sibbald R.G., Orsted H., Schultz G.S., Coutts P., Keast D. Preparing the wound bed 2003: focus on infection and inflammation. Ostomy Wound Manage 2003, 49:23-51.
5. Bowler P.G., Davies B.J. The microbiology of infected and noninfected leg ulcers. Int J Dermatol 1999, 38:573-578.
6. Trengove N.J., Stacey M.C., McGechie D.F., Mata S. Qualitative bacteriology and leg ulcer healing. J Wound Care 1996, 5:277-280.
7. Zhang Z., Schluesener H.J. Mammalian toll-like receptors: from endogenous ligands to tissue regeneration. Cell Mol Life Sci 2006, 63:2901-2907.
8. Kumar H., Kawai T., Akira S. Pathogen recognition in the innate immune response. Biochem J 2009, 420:1-16.
9. Husebye H., Halaas O., Stenmark H., Tunheim G., Sandanger O., Bogen B., et al. Endocytic pathways regulate Toll-like receptor 4 signaling and link innate and adaptive immunity. EMBO J 2006, 25:683-692.
10. Deiters U., Barsig J., Tawil B., Muhlradt P.F. The macrophage-activating lipopeptide-2 accelerates wound healing in diabetic mice. Exp Dermatol 2004, 13:731-739.
11. Koff J.L., Shao M.X., Kim S., Ueki I.F., Nadel J.A. Pseudomonas lipopolysaccharide accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 2006, 177:8693-8700.
12. Trengove N.J., Langton S.R., Stacey M.C. Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers. Wound Repair Regen 1996, 4:234-239.
13. Fivenson D.P., Faria D.T., Nickoloff B.J., Poverini P.J., Kunkel S., Burdick M., et al. Chemokine and inflammatory cytokine changes during chronic wound healing. Wound Repair Regen 1997, 5:310-322.
14. Harris I.R., Yee K.C., Walters C.E., Cunliffe W.J., Kearney J.N., Wood E.J., et al. Cytokine and protease levels in healing and non-healing chronic venous leg ulcers. Exp Dermatol 1995, 4:342-349.
15. Mast B.A., Schultz G.S. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 1996, 4:411-420.
16. Werner S., Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003, 83:835-870.
17. Braff M.H., Bardan A., Nizet V., Gallo R.L. Cutaneous defense mechanisms by antimicrobial peptides. J Invest Dermatol 2005, 125:9-13.
18. Seo S.J., Ahn J.Y., Hong C.K., Seo E.Y., Kye K.C., Lee W.H., et al. Expression of neutrophil gelatinase-associated lipocalin in skin epidermis. J Invest Dermatol 2006, 126:510-512.
19. Bando M., Hiroshima Y., Kataoka M., Shinohara Y., Herzberg M.C., Ross K.F., et al. Interleukin-1alpha regulates antimicrobial peptide expression in human keratinocytes. Immunol Cell Biol 2007, 85:532-537.
20. Flo T.H., Smith K.D., Sato S., Rodriguez D.J., Holmes M.A., Strong R.K., et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 2004, 432:917-921.
21. Yang H., Young D.W., Gusovsky F., Chow J.C. Cellular events mediated by lipopolysaccharide-stimulated toll-like receptor 4. MD-2 is required for activation of mitogen-activated protein kinases and Elk-1. J Biol Chem 2000, 275:20861-20866.
22. Chow J.C., Young D.W., Golenbock D.T., Christ W.J., Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 1999, 274:10689-10692.
23. Shimazu R., Akashi S., Ogata H., Nagai Y., Fukudome K., Miyake K., et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 1999, 189:1777-1782.
24. Flo T.H., Halaas O., Lien E., Ryan L., Teti G., Golenbock D.T., et al. Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J Immunol 2000, 164:2064-2069.
25. Pugin J., Stern-Voeffray S., Daubeuf B., Matthay M.A., Elson G., Dunn-Siegrist I. Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock. Blood 2004, 104:4071-4079.
26. Efron P.A., Moldawer L.L. Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. J Burn Care Rehabil 2004, 25:149-160.
27. Wallace H.J., Stacey M.C. Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers-correlations to healing status. J Invest Dermatol 1998, 110:292-296.
28. Mwaura B., Mahendran B., Hynes N., Defreitas D., Avalos G., Adegbola T., et al. The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and PDGF-AA on the chronicity of venous leg ulcers. Eur J Vasc Endovasc Surg 2006, 31:306-310.
29. Lien E., Ingalls R.R. Toll-like receptors. Crit Care Med 2002, 30:S1-S11.
30. Tsirogianni A.K., Moutsopoulos N.M., Moutsopoulos H.M. Wound healing: immunological aspects. Injury 2006, 37(Suppl. 1):S5-S12.
31. Cardoso L.S., Araujo M.I., Goes A.M., Pacifico L.G., Oliveira R.R., Oliveira S.C. Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis. Microb Cell Fact 2007, 6:1.
32. Trengove N.J., Bielefeldt-Ohmann H., Stacey M.C. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 2000, 8:13-25.
33. Chen W.Y., Rogers A.A. Recent insights into the causes of chronic leg ulceration in venous diseases and implications on other types of chronic wounds. Wound Repair Regen 2007, 15:434-449.
34. Sakai A., Ohshima M., Sugano N., Otsuka K., Ito K. Profiling the cytokines in gingival crevicular fluid using a cytokine antibody array. J Periodontol 2006, 77:856-864.
35. Spiekstra S.W., Breetveld M., Rustemeyer T., Scheper R.J., Gibbs S. Wound-healing factors secreted by epidermal keratinocytes and dermal fibroblasts in skin substitutes. Wound Repair Regen 2007, 15:708-717.
36. Romagnani P., Lasagni L., Annunziato F., Serio M., Romagnani S. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol 2004, 25:201-209.
37. Iocono J.A., Colleran K.R., Remick D.G., Gillespie B.W., Ehrlich H.P., Garner W.L. Interleukin-8 levels and activity in delayed-healing human thermal wounds. Wound Repair Regen 2000, 8:216-225.
38. Rennekampff H.O., Hansbrough J.F., Kiessig V., Dore C., Sticherling M., Schroder J.M. Bioactive interleukin-8 is expressed in wounds and enhances wound healing. J Surg Res 2000, 93:41-54.
39. DiPietro L.A., Burdick M., Low Q.E., Kunkel S.L., Strieter R.M. MIP-1alpha as a critical macrophage chemoattractant in murine wound repair. J Clin Invest 1998, 101:1693-1698.
40. Low Q.E., Drugea I.A., Duffner L.A., Quinn D.G., Cook D.N., Rollins B.J., et al. Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. Am J Pathol 2001, 159:457-463.
41. Hwang J., Kim C.W., Son K.N., Han K.Y., Lee K.H., Kleinman H.K., et al. Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo. FEBS Lett 2004, 570:47-51.
42. Berahovich R.D., Miao Z., Wang Y., Premack B., Howard M.C., Schall T.J. Proteolytic activation of alternative CCR1 ligands in inflammation. J Immunol 2005, 174:7341-7351.
43. Yager D.R., Nwomeh B.C. The proteolytic environment of chronic wounds. Wound Repair Regen 1999, 7:433-441.
44. Klausen P., Niemann C.U., Cowland J.B., Krabbe K., Borregaard N. On mouse and man: neutrophil gelatinase associated lipocalin is not involved in apoptosis or acute response. Eur J Haematol 2005, 75:332-340.
45. Nielsen O.H., Gionchetti P., Ainsworth M., Vainer B., Campieri M., Borregaard N., et al. Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-alpha in ulcerative colitis. Am J Gastroenterol 1999, 94:2923-2928.
46. Bauer M., Eickhoff J.C., Gould M.N., Mundhenke C., Maass N., Friedl A. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat 2008, 108:389-397.
47. Lim R., Ahmed N., Borregaard N., Riley C., Wafai R., Thompson E.W., et al. Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer: NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition. Int J Cancer 2007, 120:2426-2434.
48. Devarajan P. Neutrophil gelatinase-associated lipocalin: new paths for an old shuttle. Cancer Ther 2007, 5:463-470.
49. Tong Z., Wu X., Ovcharenko D., Zhu J., Chen C.S., Kehrer J.P. Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J 2005, 391:441-448.
50. Roudkenar M.H., Halabian R., Ghasemipour Z., Roushandeh A.M., Rouhbakhsh M., Nekogoftar M., et al. Neutrophil gelatinase-associated lipocalin acts as a protective factor against H(2)O(2) toxicity. Arch Med Res 2008, 39:560-566.
51. Roudkenar M.H., Halabian R., Roushandeh A.M., Nourani M.R., Masroori N., Ebrahimi M., et al. Lipocalin 2 regulation by thermal stresses: protective role of Lcn2/NGAL against cold and heat stresses. Exp Cell Res 2009, 315:3140-3151.
52. Chamorro C.I., Weber G., Gronberg A., Pivarcsi A., Stahle M. The human antimicrobial peptide LL-37 suppresses apoptosis in keratinocytes. J Invest Dermatol 2009, 129:937-944.
53. Heilborn J.D., Nilsson M.F., Kratz G., Weber G., Sorensen O., Borregaard N., et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol 2003, 120:379-389.
54. Cowland J.B., Sorensen O.E., Sehested M., Borregaard N. Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta, but not by TNF-alpha. J Immunol 2003, 171:6630-6639.
55. Butmarc J., Yufit T., Carson P., Falanga V. Human beta-defensin-2 expression is increased in chronic wounds. Wound Repair Regen 2004, 12:439-443.
56. Lundqvist K., Sørensen O.E., Schmidtchen A. Increased levels of human neutrophil [alpha]-defensins in chronic venous leg ulcers. J Dermatol Sci 2008, 51:131-134.
57. Vora P., Youdim A., Thomas L.S., Fukata M., Tesfay S.Y., Lukasek K., et al. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol 2004, 173:5398-5405.
58. Kluwe J., Mencin A., Schwabe R.F. Toll-like receptors, wound healing, and carcinogenesis. J Mol Med 2009, 87:125-138.
59. Ovington L. Bacterial toxins and wound healing. Ostomy Wound Manage 2003, 49:8-12.
60. White R.J., Cutting K.F. Critical colonization-the concept under scrutiny. Ostomy Wound Manage 2006, 52:50-56.
61. Hopkins P.A., Sriskandan S. Mammalian Toll-like receptors: to immunity and beyond. Clin Exp Immunol 2005, 140:395-407.