Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis
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Necrotizing enterocolitis (NEC) is a leading cause of preterm infant morbidity and mortality. Treatment for NEC is limited and non-targeted, which makes new treatment and prevention strategies critical. Host defense peptides (HDPs) are essential components of the innate immune system and have multifactorial mechanisms in host defense. LL-37 and hBD2 are two HDPs that have been shown in prior literature to protect from neonatal sepsis-induced mortality or adult inflammatory bowel disease, respectively. Therefore, this article sought to understand if these two HDPs could influence NEC severity in murine preclinical models. NEC was induced in P14-16 C57Bl/6 mice and HDPs were provided as a pretreatment or treatment. Both LL-37 and hBD2 resulted in decreased NEC injury scores as a treatment and hBD2 as a pretreatment. Our data suggest LL-37 functions through antimicrobial properties, while hBD2 functions through decreases in inflammation and improvement of intestinal barrier integrity.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 109993 |
| Tidsskrift | iScience |
| Vol/bind | 27 |
| Udgave nummer | 6 |
| Antal sider | 21 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
The authors would like to acknowledge Defensin Therapeutics for supplying the hBD2 we utilized throughout this study. The authors would also like to acknowledge Dr. Jennifer Bermick (University of Iowa) for supplying some of the LL-37 used in the wound healing assays. Finally, the authors would like to acknowledge Michele Persiani for contributions to the LL-37 wound healing data. Support for this work was provided by the NIH R01DK125415 (SJM). The study concept was performed by S.R.L. A.H.S. B.A.H.J. P.N. J.W. M.U. and S.J.M. Data acquisition, interpretation, and analysis was performed by S.R.L. A.H.S. J.N.B. H.G. B.A.H.J. T.J.B. and S.J.M. Manuscript drafting was performed by S.R.L. A.H.S. and S.J.M. Critical manuscript revision was performed by all authors. P.N. and J.W. (co-authors) are shareholders of Defensin Therapeutics ApS (DTA), Denmark. P.N. is CEO of DTA and B.J. (co-author) is next to his fulltime position as Ass. Prof. Head of Nutritional Immunology, University of Copenhagen, CSO of DTA. D.T. owns a patent to pursue the therapeutic use of hBD2 in graft versus host disease and the ethical pharmaceutical rights to pursue prophylactic or therapeutic use of hBD2 in NEC. DTA has supported this work by providing relevant amounts of hBD2. The company had no share in the data analysis, integration, and presentation. The company solely delivered the defensins used in the current study. The views expressed in this manuscript are those of the authors and not necessarily those of DTA or other funding bodies that could be construed as a potential conflict of interest.
Publisher Copyright:
© 2024 The Authors
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