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Open Access 01-12-2017 | Research article

Hepatocytes express the antimicrobial peptide HBD-2 after multiple trauma: an experimental study in human and mice

Authors: Stefanie Fitschen-Oestern, Matthias Weuster, Sebastian Lippross, Peter Behrendt, Sabine Fuchs, Thomas Pufe, Mersedeh Tohidnezhad, Andreas Bayer, Andreas Seekamp, Deike Varoga, Tim Klüter

Published in: BMC Musculoskeletal Disorders | Issue 1/2017

Abstract

Background

Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before.

In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice.

Methods

HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA. To investigate major sources of HBD-2, its expression and regulation in plasma samples, polymorphonuclear neutrophils (PMN) and human tissue samples of liver and skin were analysed by ELISA. As liver samples of trauma patients are hard to obtain we tried to review findings in an established trauma model. Plasma samples and liver samples of 56 male C57BL/6 N-mice with a thorax trauma and a femur fracture were analysed by ELISA, real-time PCR and immunohistochemistry for murine beta defensin 4 (MBD-4) and compared with the expression of control group without trauma.

The induction of HBD-2 expression in cultured hepatocytes (Hep G2) was analysed after incubation with IL-6, supernatant of Staphylococcus aureus (SA) and Lipopolysaccharides (LPS). One possible signalling pathway was tested by blocking toll-like receptor 2 (TLR2) in hepatocytes.

Results

Compared to healthy control group, plasma of multiple traumatized patients and mice showed significantly higher defensin levels after trauma. Compared to skin cells, which are known for high beta defensin expression, liver tissue showed less HBD-2 expression, but higher HBD-2 expression compared to PMN. Immunhistochemical staining demonstrated upregulated MBD-4 in hepatocytes of traumatised mice. In HepG2 cells HBD-2 expression could be increased by stimulation with IL-6 and SA. Neutralization of HepG2 cells with αTLR2 showed reduced HBD-2 expression after stimulation with SA.

Conclusion

Plasma samples of multiple traumatized patients showed high expression of HBD-2, which may protect the severely injured patient from overwhelming bacterial infection. Our data support the hypothesis that liver is one possible source for HBD-2 in plasma while posttraumatic inflammatory response.

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Title: Hepatocytes express the antimicrobial peptide HBD-2 after multiple trauma: an experimental study in human and mice
Authors: Stefanie Fitschen-Oestern
Matthias Weuster
Sebastian Lippross
Peter Behrendt
Sabine Fuchs
Thomas Pufe
Mersedeh Tohidnezhad
Andreas Bayer
Andreas Seekamp
Deike Varoga
Tim Klüter
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2017
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-017-1458-8

At a glance: The STEP trials

Springer Medicine

Hepatocytes express the antimicrobial peptide HBD-2 after multiple trauma: an experimental study in human and mice

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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