학술논문
Insulin Can Delay Neutrophil Extracellular Trap Formation In Vitro-Implication for Diabetic Wound Care?
Document Type
Academic Journal
Author
Linnemann C; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Şahin F; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Li N; Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Pscherer S; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Department of Internal Medicine III, Sophien- and Hufeland-Hospital, 99425 Weimar, Germany.; Götz F; Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Histing T; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Nussler AK; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.; Ehnert S; Siegfried Weller Institute for Trauma Research, BG Unfallklinik Tübingen, Eberhard Karls Universität Tuebingen, 72076 Tuebingen, Germany.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101587988 Publication Model: Electronic Cited Medium: Print ISSN: 2079-7737 (Print) Linking ISSN: 20797737 NLM ISO Abbreviation: Biology (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2079-7737
Abstract
Diabetes is a worldwide evolving disease with many associated complications, one of which is delayed or impaired wound healing. Appropriate wound healing strongly relies on the inflammatory reaction directly after injury, which is often altered in diabetic wound healing. After an injury, neutrophils are the first cells to enter the wound site. They have a special defense mechanism, neutrophil extracellular traps (NETs), consisting of released DNA coated with antimicrobial proteins and histones. Despite being a powerful weapon against pathogens, NETs were shown to contribute to impaired wound healing in diabetic mice and are associated with amputations in diabetic foot ulcer patients. The anti-diabetic drugs metformin and liraglutide have already been shown to regulate NET formation. In this study, the effect of insulin was investigated. NET formation after stimulation with PMA (phorbol myristate acetate), LPS (lipopolysaccharide), or calcium ionophore (CI) in the presence/absence of insulin was analyzed. Insulin led to a robust delay of LPS- and PMA-induced NET formation but had no effect on CI-induced NET formation. Mechanistically, insulin induced reactive oxygen species, phosphorylated p38, and ERK, but reduced citrullination of histone H3. Instead, bacterial killing was induced. Insulin might therefore be a new tool for the regulation of NET formation during diabetic wound healing, either in a systemic or topical application.