The Role of Chemokines in Wound Healing - PubMed (original) (raw)

Review

The Role of Chemokines in Wound Healing

Anisyah Ridiandries et al. Int J Mol Sci. 2018.

Abstract

Wound healing is a multistep process with four overlapping but distinct stages: hemostasis, inflammation, proliferation, and remodeling. An alteration at any stage may lead to the development of chronic non-healing wounds or excessive scar formation. Impaired wound healing presents a significant health and economic burden to millions of individuals worldwide, with diabetes mellitus and aging being major risk factors. Ongoing understanding of the mechanisms that underly wound healing is required for the development of new and improved therapies that increase repair. Chemokines are key regulators of the wound healing process. They are involved in the promotion and inhibition of angiogenesis and the recruitment of inflammatory cells, which release growth factors and cytokines to facilitate the wound healing process. Preclinical research studies in mice show that the administration of CCL2, CCL21, CXCL12, and a CXCR4 antagonist as well as broad-spectrum inhibition of the CC-chemokine class improve the wound healing process. The focus of this review is to highlight the contributions of chemokines during each stage of wound healing and to discuss the related molecular pathologies in complex and chronic non-healing wounds. We explore the therapeutic potential of targeting chemokines as a novel approach to overcome the debilitating effects of impaired wound healing.

Keywords: angiogenesis; chemokine; healing; inflammation; wound.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Chemokines in early and late phases of wound healing. (a) Early wound healing, including clot formation, inflammation, and proliferation. (1) Clot formation occurs to prevent the loss of blood and (2) platelets are activated and release (3) α-granules, which in turn release (4) CXCL4 as an early inhibitor of angiogenesis. Once the clot has fully formed other, chemokines such as CXCL8, CXCL1, and CXCL2 are released by α-granules to recruit inflammatory cells, including (5) neutrophils and (6) macrophages. Neutrophils are increased early in the healing process, then macrophages soon take over as the primary inflammatory cell. Neutrophils and macrophages release (7) chemokines such as CCL2, CCL3, and CCL5 into the wound to promote the recruitment of more inflammatory cells that release pro-angiogenic growth factors that (8) increase neovessel formation in the wound. (b) Late wound healing is the remodeling stage. In this stage, the wound is fully healed and (1) a scar has formed. Type 3 collagen converts to (2) type 1 collagen to promote scar formation and create a more stable wound seal. During the remodeling process (3), angiostatic chemokines (CXCL10, CXCL11) promote the (4) regression of neovessels, as there is no longer a requirement for enhanced blood flow or the recruitment of immunological cells to the site. ↓: indicates decrease;↑: indicates decrease.

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References

    1. Tonnesen M.G., Feng X., Clark R.A. Angiogenesis in wound healing. J. Investig. Dermatol. Symp. Proc. 2000;5:40–46. doi: 10.1046/j.1087-0024.2000.00014.x. - DOI - PubMed
    1. Kufareva I., Salanga C.L., Handel T.M. Chemokine and chemokine receptor structure and interactions: Implications for therapeutic strategies. Immunol. Cell Biol. 2015;93:372–383. doi: 10.1038/icb.2015.15. - DOI - PMC - PubMed
    1. Gleissner C.A., von Hundelshausen P., Ley K. Platelet chemokines in vascular disease. Arterioscler. Thromb. Vasc. Biol. 2008;28:1920–1927. doi: 10.1161/ATVBAHA.108.169417. - DOI - PMC - PubMed
    1. Engelhardt E., Toksoy A., Goebeler M., Debus S., Brocker E.B., 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. 1998;153:1849–1860. doi: 10.1016/S0002-9440(10)65699-4. - DOI - PMC - PubMed
    1. Kobayashi Y. The role of chemokines in neutrophil biology. Front. Biosci. 2008;13:2400–2407. doi: 10.2741/2853. - DOI - PubMed

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