Repair of wounded tissue is a complex sequence of events, initiated by platelet aggregation and fibrin polymerisation, followed by infiltration of leukocytes. Wound repair is connected with increased angiogenesis. Beside hypoxia, mediators such as FGF and VEGF, antimicrobial peptides likely play a role in the regulation of wound repair. Cathelicidin peptides have pleotropic effects on different processes involved. LL-37 regulates epithelial cell proliferation and wound closure (Figure 2). Angiogenesis is an essential part of host defense, regeneration, and repair.
It is not completely understood how AMPs integrate into existing networks of angiogenetic factors. Hypoxia inducible factor-1 (HIF-1) is a central component of the oxygen sensing system that coordinates cellular responses to conditions of decreased oxygen availability. It has been demonstrated for the murine system that expression of the cathelicidin peptide CRAMP is regulated by. This demonstrated an additional link between the angiogenesis and host defense systems. The association between AMPs and classical angiogenetic mediators such as FGF or VEGF has not been developed.
Neutrophils angiogenesis regulation of inflammation
Figure 2. Overview on the functions of AMPs in wound healing. AMPs are produced by host defense cells such as neutrophils and macrophages and epithelial cells. They act as endogenous antibiotic and also influence angiogenesis, wound healing and inflammatory processes
The activities of AMPs described in this article suggest that these peptides might also have a role in tumor biology. AMPs were found increased in several cancer types such as oral carcinomas, breast cancer, cervical and vulval carcinoma. The human cathelicidin LL-37 was found highly expressed in breast cancer cells. The highest levels were found in high grade tumors. Further studies are required to elucidate the functions of AMPs in cancer, but a multifunctional role of AMPs is becoming increasingly manifest.
Angiogenesis is an essential part of inflammation, wound repair and tumor growth. The network between cytokines, growth factors, AMPs is not completely understood so far but it is obvious that AMPs contribute in a relevant way to that meshwork. Further work sure will identify the role of AMPs more clearly.
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