Skip to main content
SpringerLink
Log in

The Role of Chemokines in Fibrotic Dermal Remodeling and Wound Healing

  • Chapter
  • First Online:
Fibrosis in Disease

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

The skin is an essential part of the integumentary organ system, providing protection from pathogens, allowing for water and electrolyte homeostasis, and relaying sensory information from the surroundings. Skin has a sophisticated and orderly architecture of dermal layers, each containing a unique mixture of cell populations, specialized structures, and extracellular matrix components. Following wounding, the dermis undergoes a highly ordered process of repair that consists of overlapping phases of hemostasis and inflammation, proliferation and angiogenesis, and remodeling of the nascent tissue. The activities of chemokines largely orchestrate this healing process. These small cytokines act through various receptors and effects on the extracellular matrix to coordinate migration, survival, and other cellular processes. Several of these chemokine signaling pathways influence the inflammatory cascade early on in healing and the later growth and regression of neovasculature, re-epithelializaiton of the wound area, and ultimately are essential for providing cues when the repair process should halt the process is complete.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kolarsick PA, Ann Kolarsick M, Goodwin C. Anatomy and physiology of the skin. [cited 2018 Feb 9]; Available from: https://www.nursingcenter.com/journalarticle?Article_ID=1207477&Journal_ID=849729&Issue_ID=1207454.

  2. Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol [Internet]. 2011 [cited 2018 Feb 12];12(9):565–80. Available from: http://www.nature.com/articles/nrm3175.

    Article  CAS  Google Scholar 

  3. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol [Internet]. 1994;130(4):489–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8166487.

    Article  CAS  Google Scholar 

  4. Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care. Adv Skin Wound Care [Internet]. 2012 [cited 2018 Feb 24];25(7):304–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22713781.

    Article  Google Scholar 

  5. Flanagan M. Wound Healing and Skin Integrity: Principles and Practice, First Edition. Edited by Madeleine Flanagan. ©2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd. p. 314.

    Google Scholar 

  6. Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. Gerontology [Internet]. 2013 [cited 2018 Jan 29];59(2):159–64. Available from: https://www.karger.com/Article/FullText/342344.

    Article  Google Scholar 

  7. Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients [Internet]. 2017 [cited 2018 Jan 29];9(8):866. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28805671.

  8. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res [Internet]. 2010 [cited 2018 Jan 29];89(3):219–29. Available from: http://journals.sagepub.com/doi/10.1177/0022034509359125.

    Article  CAS  Google Scholar 

  9. Rodero MP, Khosrotehrani K. Skin wound healing modulation by macrophages. Int J Clin Exp Pathol [Internet]. 2010 [cited 2018 Feb 12];3(7):643–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20830235.

  10. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol [Internet]. 2007 [cited 2018 Feb 12];25(1):9–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17276196.

    Article  CAS  Google Scholar 

  11. Carmeliet P. Angiogenesis in health and disease. Nat Med [Internet]. 2003 [cited 2018 Feb 17];9(6):653–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12778163.

    Article  CAS  Google Scholar 

  12. Rowlatt U. Intrauterine wound healing in a 20 week human fetus. Virchows Arch A Pathol Anat Histol [Internet]. 1979;381(3):353–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/155931.

  13. Armstrong JR, Ferguson MWJ. Ontogeny of the skin and the transition from scar-free to scarring phenotype during wound healing in the pouch young of a marsupial, Monodelphis domestica. Dev Biol [Internet]. 1995 [cited 2018 Feb 17];169(1):242–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7750642.

    Article  CAS  Google Scholar 

  14. Yates CC, Hebda P, Wells A. Skin wound healing and scarring: fetal wounds and regenerative restitution. Birth Defects Res C Embryo Today [Internet]. 2012;96(4):325–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24203921.

    Article  CAS  Google Scholar 

  15. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol [Internet]. 2008 [cited 2017 Dec 1];214(2):199–210. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18161745

    Article  CAS  Google Scholar 

  16. Bayat A, McGrouther DA, Ferguson MWJ. Skin scarring. BMJ [Internet]. 2003 [cited 2018 Feb 17];326(7380):88–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12521975.

  17. Calderon M, Lawrence WT, Banes AJ. Increased proliferation in keloid fibroblasts wounded in vitro. J Surg Res [Internet]. 1996 [cited 2018 Jan 29];61(2):343–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0022480496901274

    Article  CAS  Google Scholar 

  18. Diegelmann RF, Cohen IK, McCoy BJ. Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro. J Cell Physiol [Internet]. 1979 [cited 2018 Jan 29];98(2):341–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/422662

    Article  CAS  Google Scholar 

  19. Corr DT, Hart DA. Biomechanics of scar tissue and uninjured skin. Adv Wound Care [Internet]. 2013 [cited 2018 Jan 29];2(2):37–43. Available from: http://online.liebertpub.com/doi/abs/10.1089/wound.2011.0321.

    Article  Google Scholar 

  20. Brown KD, Zurawski SM, Mosmann TR, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol [Internet]. 1989 [cited 2018 Feb 16];142(2):679–87. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2521353.

  21. Cochran BH, Reffel AC, Stiles CD. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell [Internet]. 1983 [cited 2018 Feb 16];33(3):939–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6872001.

  22. Sherry B, Cerami A. Small cytokine superfamily. Curr Opin Immunol [Internet]. 1991 [cited 2018 Feb 16];3(1):56–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2054114.

    Article  CAS  Google Scholar 

  23. Poplawsky A, Niewiarowaki S. Dissociation of platelet antiheparin factor (platelet factor 4) from lipoprotein lipase inhibitor. Biochim Biophys Acta [Internet]. 1964 [cited 2018 Feb 16];90:403–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14220728.

  24. Oppenheim JJ, Zachariae COC, Mukaida N, Matsushima K. Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu Rev Immunol [Internet]. 1991 [cited 2018 Feb 16];9(1):617–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1910690

    Article  CAS  Google Scholar 

  25. Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol [Internet]. 1987 [cited 2018 Feb 17];139(3):788–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3298433.

  26. Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev [Internet]. 2000 [cited 2018 Feb 17];52(1):145–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10699158.

  27. Van Damme J, Van Beeumen J, Opdenakker G, Billiau A. A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil chemotactic, skin-reactive, and granulocytosis-promoting activity. J Exp Med [Internet]. 1988 [cited 2018 Feb 17];167(4):1364–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3258625.

  28. Walz A, Peveri P, Aschauer H, Baggiolini M. Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun [Internet]. 1987 [cited 2018 Feb 17];149(2):755–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3322281.

    Article  CAS  Google Scholar 

  29. Larsen CG, Anderson AO, Appella E, Oppenheim JJ, Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science [Internet]. 1989 [cited 2018 Feb 17];243(4897):1464–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2648569.

    Article  CAS  Google Scholar 

  30. Yoshimura T, Robinson EA, Tanaka S, Appella E, Leonard EJ. Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J Immunol [Internet]. 1989;142(6):1956–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2921521.

  31. Matsushima K, Larsen CG, DuBois GC, Oppenheim JJ. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med [Internet]. 1989 [cited 2018 Feb 17];169(4):1485–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2926331.

    Article  CAS  Google Scholar 

  32. Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol [Internet]. 2001;2(2):102–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11175801.

    Article  CAS  Google Scholar 

  33. Wolf M, Moser B. Antimicrobial activities of chemokines: not just a side-effect? Front Immunol [Internet]. 2012 [cited 2018 Feb 17];3:213. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22837760.

  34. Park PS-H, Lodowski DT, Palczewski K. Activation of G protein–coupled receptors: beyond two-state models and tertiary conformational changes. Annu Rev Pharmacol Toxicol [Internet]. 2008 [cited 2018 Feb 7];48(1):107–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17848137.

  35. Kufareva I, Salanga CL, Handel TM. Chemokine and chemokine receptor structure and interactions: implications for therapeutic strategies. Immunol Cell Biol [Internet]. 2015 [cited 2018 Feb 7];93(4):372–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25708536.

    Article  CAS  Google Scholar 

  36. Mizoue LS, Bazan JF, Johnson EC, Handel TM. Solution structure and dynamics of the CX 3 C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX 3 CR1 †, ‡. Biochemistry [Internet]. 1999 [cited 2018 Feb 7];38(5):1402–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9931005.

  37. Tuinstra RL, Peterson FC, Kutlesa S, Elgin ES, Kron MA, Volkman BF. Interconversion between two unrelated protein folds in the lymphotactin native state. Proc Natl Acad Sci [Internet]. 2008 [cited 2018 Feb 7];105(13):5057–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18364395.

    Article  CAS  Google Scholar 

  38. Paavola CD, Hemmerich S, Grunberger D, Polsky I, Bloom A, Freedman R, et al. Monomeric monocyte chemoattractant protein-1 (MCP-1) binds and activates the MCP-1 receptor CCR2B. J Biol Chem [Internet]. 1998 [cited 2018 Feb 7];273(50):33157–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9837883.

    Article  CAS  Google Scholar 

  39. Rajarathnam K, Sykes BD, Kay CM, Dewald B, Geiser T, Baggiolini M, et al. Neutrophil activation by monomeric interleukin-8. Science [Internet]. 1994 [cited 2018 Feb 7];264(5155):90–2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8140420.

    Article  CAS  Google Scholar 

  40. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270:27348–57.

    Article  CAS  Google Scholar 

  41. Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, et al. CXC chemokines in angiogenesis. J Leukoc Biol [Internet]. 2000;68(1):1–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10914483.

  42. Nomiyama H, Yoshie O. Functional roles of evolutionary conserved motifs and residues in vertebrate chemokine receptors. J Leukoc Biol [Internet]. 2015 [cited 2018 Feb 24];97(1):39–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25416815.

    Article  Google Scholar 

  43. Viola A, Luster AD. Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol [Internet]. 2008;48(1):171–97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17883327.

    Article  CAS  Google Scholar 

  44. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S. Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett [Internet]. 2002 [cited 2018 Feb 7];520(1–3):97–101. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12044878.

    Article  CAS  Google Scholar 

  45. Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol [Internet]. 2008 [cited 2018 Feb 7];9(1):60–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18043707.

    Article  CAS  Google Scholar 

  46. Ulvmar MH, Hub E, Rot A. Atypical chemokine receptors. Exp Cell Res [Internet]. 2011 [cited 2018 Jan 29];317(5):556–68. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21272574.

    Article  CAS  Google Scholar 

  47. Nomiyama H, Osada N, Yoshie O. A family tree of vertebrate chemokine receptors for a unified nomenclature. Dev Comp Immunol [Internet]. 2011 [cited 2018 Jan 29];35(7):705–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21295066.

    Article  CAS  Google Scholar 

  48. Nibbs R, Graham G, Rot A. Chemokines on the move: control by the chemokine “interceptors” Duffy blood group antigen and D6. Semin Immunol [Internet]. 2003 [cited 2018 Jan 29];15(5):287–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15001178.

  49. Mantovani A, Bonecchi R, Locati M. Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol [Internet]. 2006 [cited 2018 Jan 29];6(12):907–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17124512.

    Article  CAS  Google Scholar 

  50. Pruenster M, Mudde L, Bombosi P, Dimitrova S, Zsak M, Middleton J, et al. The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. Nat Immunol [Internet]. 2009 [cited 2018 Jan 29];10(1):101–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19060902.

    Article  Google Scholar 

  51. Hamel DJ, Sielaff I, Proudfoot AEI, Handel TM. Chapter 4 interactions of chemokines with glycosaminoglycans. In: Methods Enzymol [Internet]. 2009 [cited 2018 Feb 17]. p. 71–102. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19480915.

    Google Scholar 

  52. Proudfoot AEI, Johnson Z, Bonvin P, Handel TM. Glycosaminoglycan interactions with chemokines add complexity to a complex system. pharmaceuticals (Basel) [Internet]. 2017 [cited 2018 Feb 24];10(3). Available from: http://www.ncbi.nlm.nih.gov/pubmed/28792472.

  53. Piepkorn MW. Dansyl (5-dimethylaminonaphthalene-1-sulphonyl)-heparin binds antithrombin III and platelet factor 4 at separate sites. Biochem J [Internet]. 1981 [cited 2018 Feb 16];196(2):649–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7317004.

    Article  CAS  Google Scholar 

  54. Scully MF, Weerasinghe K, Kakkar V V. Inhibition of contact activation by platelet factor 4. Thromb Res [Internet]. 1980 [cited 2018 Feb 16];20(4):461–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6163223.

    Article  CAS  Google Scholar 

  55. Dumenco LL, Everson B, Culp LA, Ratnoff OD. Inhibition of the activation of Hageman factor (factor XII) by platelet factor 4. J Lab Clin Med [Internet]. 1988 [cited 2018 Feb 16];112(3):394–400. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3045234.

  56. Griffin JH, Fernández JA, Gale AJ, Mosnier LO. Activated protein C. J Thromb Haemost [Internet]. 2007 [cited 2018 Feb 16];5(s1):73–80. Available from: http://doi.wiley.com/10.1111/j.1538-7836.2007.02491.x.

  57. Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, et al. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science [Internet]. 1990 [cited 2018 Feb 16];247(4938):77–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1688470.

    Article  CAS  Google Scholar 

  58. Watson JB, Getzler SB, Mosher DF. Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor. J Clin Invest [Internet]. 1994 [cited 2018 Feb 16];94(1):261–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8040268.

    Article  CAS  Google Scholar 

  59. Gengrinovitch S, Greenberg SM, Cohen T, Gitay-Goren H, Rockwell P, Maione TE, et al. Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms. J Biol Chem [Internet]. 1995 [cited 2018 Feb 16];270(25):15059–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7797488

    Article  CAS  Google Scholar 

  60. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003;197:1537–49.

    Article  CAS  Google Scholar 

  61. Aidoudi S, Bikfalvi A. Interaction of PF4 (CXCL4) with the vasculature: a role in atherosclerosis and angiogenesis. Thromb Haemost [Internet]. 2010 [cited 2018 Jan 16];104(5):941–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20806113.

  62. Bebawy ST, Gorka J, Hyers TM, Webster RO. In vitro effects of platelet factor 4 on normal human neutrophil functions. J Leukoc Biol [Internet]. 1986 [cited 2018 Feb 16];39(4):423–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3005456.

    Article  CAS  Google Scholar 

  63. Han ZC, Sensébe L, Abgrall JF, Brière J. Platelet factor 4 inhibits human megakaryocytopoiesis in vitro. Blood [Internet]. 1990 [cited 2018 Feb 16];75(6):1234–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2310823.

  64. Lambert MP, Rauova L, Bailey M, Sola-Visner MC, Kowalska MA, Poncz M. Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications. Blood [Internet]. 2007 [cited 2018 Feb 16];110(4):1153–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17495129.

    Article  CAS  Google Scholar 

  65. Dudek AZ, Nesmelova I, Mayo K, Verfaillie CM, Pitchford S, Slungaard A. Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8: novel mechanisms for modulation of hematopoiesis. Blood [Internet]. 2003 [cited 2018 Feb 16];101(>12):4687–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586630.

    Article  CAS  Google Scholar 

  66. Engelhardt E, Toksoy A, Goebeler M, Debus S, Bröcker EB, Gillitzer R. Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am J Pathol [Internet]. 1998;153(6):1849–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9846975.

  67. Martins-Green M, Petreaca M, Wang L. Chemokines and their receptors are key players in the orchestra that regulates wound healing. Adv Wound Care [Internet]. 2013;2(7):327–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24587971.

    Article  Google Scholar 

  68. Conus S, Perozzo R, Reinheckel T, Peters C, Scapozza L, Yousefi S, et al. Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. J Exp Med [Internet]. 2008;205(3):685–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18299403.

    Article  CAS  Google Scholar 

  69. Petreaca ML, Yao M, Liu Y, DeFea K, Martins-Green M. Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8/CXCL8) is required for IL-8/CXCL8-induced endothelial permeability. Mol Biol Cell [Internet]. 2007;18(12):5014–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17928406.

    Article  CAS  Google Scholar 

  70. Hurst SM, Wilkinson TS, McLoughlin RM, Jones S, Horiuchi S, Yamamoto N, et al. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity [Internet]. 2001 [cited 2018 Feb 24];14(6):705–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11420041.

  71. Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing. J Leukoc Biol [Internet]. 2001;69(4):513–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11310836.

  72. Henderson RB, Hobbs JAR, Mathies M, Hogg N. Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. Blood [Internet]. 2003 [cited 2018 Feb 24];102(1):328–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12623845.

    Article  CAS  Google Scholar 

  73. Juremalm M, Nilsson G. Chemokine receptor expression by mast cells. In: Mast cells in allergic diseases [Internet]. Basel: KARGER; 2005 [cited 2018 Feb 24]. p. 130–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16107768.

    Chapter  Google Scholar 

  74. Gharaee-Kermani M, Denholm EM, Phan SH. Costimulation of fibroblast collagen and transforming growth factor beta1 gene expression by monocyte chemoattractant protein-1 via specific receptors. J Biol Chem [Internet]. 1996;271:17779–84. Available from: https://doi.org/10.1074/jbc.271.30.17779.

    Article  CAS  Google Scholar 

  75. Yamamoto T, Eckes B, Mauch C, Hartmann K, Krieg T. Monocyte chemoattractant protein-1 enhances gene expression and synthesis of matrix metalloproteinase-1 in human fibroblasts by an autocrine IL-1 alpha loop. J Immunol. 2000;164:6174–9.

    Article  CAS  Google Scholar 

  76. Feugate JE, Li Q, Wong L, Martins-Green M. The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure. J Cell Biol [Internet]. 2002;156(1):161–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11781340.

    Article  CAS  Google Scholar 

  77. Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, et al. Epithelialization in wound healing: a comprehensive review. Adv Wound Care [Internet]. 2014 [cited 2018 Feb 24];3(7):445–64. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25032064.

    Article  Google Scholar 

  78. Devalaraja RM, Nanney LB, Qian Q, Du J, Yu Y, Devalaraja MN, et al. Delayed wound healing in CXCR2 knockout mice. J Invest Dermatol [Internet]. 2000;115(2):234–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10951241.

    Article  CAS  Google Scholar 

  79. Satish L, Blair HC, Glading A, Wells A. Interferon-inducible protein 9 (CXCL11)-induced cell motility in keratinocytes requires calcium flux-dependent activation of -calpain. Mol Cell Biol [Internet]. 2005;25(5):1922–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15713646.

    Article  CAS  Google Scholar 

  80. Chakera A, Seeber RM, John AE, Eidne KA, Greaves DR, Rodríguez-Frade JM, et al. A new class of membrane-bound chemokine with a CX3C motif. Gluud LL, editor. J Immunol [Internet]. 2008 [cited 2017 Nov 28];19(1):1. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22236446.

  81. Yates CC, Whaley D, Hooda S, Hebda PA, Bodnar RJ, Wells A. Delayed reepithelialization and basement membrane regeneration after wounding in mice lacking CXCR3. Wound Repair Regen [Internet]. 2009;17(1):34–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19152649.

    Article  Google Scholar 

  82. Grotendorst GR, Rahmanie H, Duncan MR. Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation. FASEB J [Internet]. 2004;18(3):469–79. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15003992.

    Article  CAS  Google Scholar 

  83. Bride J, Viennet C, Lucarz-Bietry A, Humbert P. Indication of fibroblast apoptosis during the maturation of disc-shaped mechanically stressed collagen lattices. Arch Dermatol Res [Internet]. 2004;295(8–9):312–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14652775.

    Article  Google Scholar 

  84. Shiraha H, Glading A, Gupta K, Wells A. IP-10 inhibits epidermal growth factor-induced motility by decreasing epidermal growth factor receptor-mediated calpain activity. J Cell Biol. 1999;146(1):243–54.

    Article  CAS  Google Scholar 

  85. Bodnar RJ, Yates CC, Wells A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res [Internet]. 2006 [cited 2017 Nov 28];98(5):617–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16484616.

    Article  CAS  Google Scholar 

  86. Bodnar RJ, Yates CC, Rodgers ME, Du X, Wells A. IP-10 induces dissociation of newly formed blood vessels. J Cell Sci [Internet]. 2009 [cited 2017 Nov 28];122(12):2064–77. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19470579.

    Article  CAS  Google Scholar 

  87. Yates CC, Whaley D, Kulasekeran P, Hancock WW, Lu B, Bodnar R, et al. Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor. Am J Pathol [Internet]. 2007;171(2):484–95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17600132.

    Article  CAS  Google Scholar 

  88. Yates CC, Krishna P, Whaley D, Bodnar R, Turner T, Wells A. Lack of CXC chemokine receptor 3 signaling leads to hypertrophic and hypercellular scarring. Am J Pathol [Internet]. 2010;176(4):1743–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20203286.

    Article  Google Scholar 

  89. Yates CC, Whaley D, Wells A. Transplanted fibroblasts prevents dysfunctional repair in a murine CXCR3-deficient scarring model. Cell Transplant [Internet]. 2012;21(5):919–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22236446.

    Article  Google Scholar 

  90. Hocking AM. The role of chemokines in mesenchymal stem cell homing to wounds. Adv Wound Care [Internet]. 2015 [cited 2018 Feb 24];4(11):623–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26543676.

    Article  Google Scholar 

  91. Feng G, Hao D, Chai J. Processing of CXCL12 impedes the recruitment of endothelial progenitor cells in diabetic wound healing. FEBS J [Internet]. 2014 [cited 2018 Feb 24];281(22):5054–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25211042.

    Article  CAS  Google Scholar 

  92. Sahin H, Wasmuth HE. Chemokines in tissue fibrosis. Biochim Biophys Acta. 2013;1832(7):1041–8. https://doi.org/10.1016/j.bbadis.2012.11.004. PubMed PMID: 23159607.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Promotion and Development, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA

    Zariel I. Johnson, Jun Heo, Erin Frankel, Dana R. Julian & Cecelia C. Yates

  2. Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA

    Christopher Mahoney

  3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Cecelia C. Yates

Authors
  1. Zariel I. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher Mahoney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Heo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erin Frankel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dana R. Julian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cecelia C. Yates
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cecelia C. Yates .

Editor information

Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indiana Center for Musculoskeletal Health, Indianapolis, IN, USA

    Monte S. Willis

  2. Department of Health Promotion and Development, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA

    Cecelia C. Yates

  3. Department of Pharmacology and Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Jonathan C. Schisler

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Johnson, Z.I., Mahoney, C., Heo, J., Frankel, E., Julian, D.R., Yates, C.C. (2019). The Role of Chemokines in Fibrotic Dermal Remodeling and Wound Healing. In: Willis, M., Yates, C., Schisler, J. (eds) Fibrosis in Disease . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98143-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-98143-7_1

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-98142-0

  • Online ISBN: 978-3-319-98143-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation