University of Oulu

Jaurila et al. J Transl Med (2017) 15:11, DOI 10.1186/s12967-016-1110-7

Inhibitory effects of serum from sepsis patients on epithelial cell migration in vitro : a case control study

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Author: Jaurila, Henna1,2; Koivukangas, Vesa1; Koskela, Marjo1;
Organizations: 1Research Group of Surgery, Anesthesia and Intensive Care, Oulu University Hospital
2Cancer and Translational Medicine Research Unit, Faculty of Medicine, Medical Research Center Oulu, University of Oulu
3Research Group of Biomedicine, Faculty of Biochemistry and Molecular Medicine, University of Oulu
4Research Unit of Biomedicine, Faculty of Medicine and Biocenter of Oulu, University of Oulu
5Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences
6Research Group of Oral Health Sciences, Oulu University Hospital, Medical Research Center Oulu, University of Oulu
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2017-03-30


Background: Sepsis delays wound re-epithelialization. In this study we explored the effect of human sepsis sera as well as the effects of cytokines, growth factors and exosomes of sepsis sera treated normal fibroblasts (NF) on keratinocyte migration and proliferation in vitro.

Methods: Serum samples were taken on days 1, 4, and 9 from 44 patients diagnosed with severe sepsis, and from 14 matching healthy controls. We evaluated the effects of sepsis serum with or without TNF-α, EGF, EGF receptor inhibitor or exosomes of sepsis sera treated NF on human keratinocyte (HaCaT) proliferation (BrdU assay), viability (MTT assay), and migration (horizontal wound healing model). Cytokine levels of sepsis and healthy sera were measured by multiplex assay. Comparisons between groups were carried out using SPSS statistics and P < 0.05 was considered significant.

Results: Severe-sepsis sera collected on days 1, 4, and 9 reduced keratinocyte proliferation by 6% (P = 0.005), 20% (P = 0.001), and 18% (P = 0.002), respectively, compared to control sera. Cell viability in cultures exposed to sepsis sera from days 4 and 9 was reduced by 38% (P = 0.01) and 58% (P < 0.001), respectively. Open-surface wounds exposed to sepsis sera from days 1 and 4 were larger than those exposed to sera from healthy controls (60 vs. 31%, P = 0.034 and 66 vs. 31%, P = 0.023, respectively). Exosomes of sepsis or healthy sera treated NF inhibited keratinocyte migration. We detected higher serum levels of cytokines TNF-α (5.7 vs. 0.7 pg/ml, P < 0.001), IL-6 (24.8 vs. 3.8 pg/ml, P < 0.001), IL-10 (30.0 vs. 11.9 pg/ml, P = 0.040), and VEGF (177.9 vs. 48.1 pg/ml, P = 0.018) in sepsis sera. Levels of EGF were significantly lower in sepsis sera than in that of healthy controls (6.5 vs. 115.6 pg/ml, P < 0.001). Sepsis serum supplemented with EGF 5 ng/ml and TNF-α in all concentrations improved keratinocyte migration.

Conclusions: Keratinocyte viability, proliferation and migration were reduced in severe sepsis in vitro. Exosomes from NF added in healthy or sepsis serum media inhibited keratinocyte migration. Decreased levels of EGF in sepsis sera may partially explain the delay of wound healing with severe-sepsis patients. Increased levels of TNF-α in sepsis sera do not explain diminished keratinocyte migration.

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Series: Journal of translational medicine
ISSN: 1479-5876
ISSN-E: 1479-5876
ISSN-L: 1479-5876
Volume: 15
Article number: 11
DOI: 10.1186/s12967-016-1110-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3126 Surgery, anesthesiology, intensive care, radiology
Funding: This study was supported by grants from the Medical Research Center of Oulu, University of Oulu Graduate School, the Finnish Medical Foundation, and the Finnish Cultural Foundation, Lapland Regional Fund.
Dataset Reference: The datasets supporting the conclusions of this article are included within the article.
Copyright information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.