Thomas Damgaard Sandahl

The damage-associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation

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The damage-associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation. / Laursen, Tea Lund; Støy, Sidsel; Deleuran, Bent et al.

In: A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica, Vol. 124, No. 9, 06.2016, p. 741-7.

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@article{cf2bfdef5837465297d43c24c4abaf87,
title = "The damage-associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation",
abstract = "The role of sterile inflammation caused by release of damage-associated molecular patterns (DAMP) remains unclear in human alcoholic hepatitis (AH). The DAMP, high mobility group box-1 protein (HMGB1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB1 is a primary inflammatory driver in AH by determining HMGB1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB1 in 34 AH patients and 10 healthy controls using ELISA. Toll-like receptor 4 (TLR4) and CD14 expressions were assessed by flow cytometry on HMGB1-stimulated peripheral blood mononuclear cells (PBMC) and ELISA was used to measure TNF-α and IL-1β in the supernatants. We observed 5-fold higher serum levels of HMGB1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB1 stimulation increased the expression of TLR4 on CD14+-monocytes compared with unstimulated cells in the AH patients. The TNF-α and IL-1β production in response to HMGB1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB1 in their blood. This combined with an increased TLR4 expression, but an unaffected cytokine response to HMGB1 suggest that HMGB1 is not the primary driver of inflammation in AH.",
keywords = "Journal Article",
author = "Laursen, {Tea Lund} and Sidsel St{\o}y and Bent Deleuran and Hendrik Vilstrup and Henning Gr{\o}nbaek and Sandahl, {Thomas Damgaard}",
note = "{\textcopyright} 2016 APMIS. Published by John Wiley & Sons Ltd.",
year = "2016",
month = jun,
doi = "10.1111/apm.12568",
language = "English",
volume = "124",
pages = "741--7",
journal = "A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica",
issn = "0903-4641",
publisher = "Wiley Online",
number = "9",

}

RIS

TY - JOUR

T1 - The damage-associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation

AU - Laursen, Tea Lund

AU - Støy, Sidsel

AU - Deleuran, Bent

AU - Vilstrup, Hendrik

AU - Grønbaek, Henning

AU - Sandahl, Thomas Damgaard

N1 - © 2016 APMIS. Published by John Wiley & Sons Ltd.

PY - 2016/6

Y1 - 2016/6

N2 - The role of sterile inflammation caused by release of damage-associated molecular patterns (DAMP) remains unclear in human alcoholic hepatitis (AH). The DAMP, high mobility group box-1 protein (HMGB1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB1 is a primary inflammatory driver in AH by determining HMGB1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB1 in 34 AH patients and 10 healthy controls using ELISA. Toll-like receptor 4 (TLR4) and CD14 expressions were assessed by flow cytometry on HMGB1-stimulated peripheral blood mononuclear cells (PBMC) and ELISA was used to measure TNF-α and IL-1β in the supernatants. We observed 5-fold higher serum levels of HMGB1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB1 stimulation increased the expression of TLR4 on CD14+-monocytes compared with unstimulated cells in the AH patients. The TNF-α and IL-1β production in response to HMGB1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB1 in their blood. This combined with an increased TLR4 expression, but an unaffected cytokine response to HMGB1 suggest that HMGB1 is not the primary driver of inflammation in AH.

AB - The role of sterile inflammation caused by release of damage-associated molecular patterns (DAMP) remains unclear in human alcoholic hepatitis (AH). The DAMP, high mobility group box-1 protein (HMGB1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB1 is a primary inflammatory driver in AH by determining HMGB1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB1 in 34 AH patients and 10 healthy controls using ELISA. Toll-like receptor 4 (TLR4) and CD14 expressions were assessed by flow cytometry on HMGB1-stimulated peripheral blood mononuclear cells (PBMC) and ELISA was used to measure TNF-α and IL-1β in the supernatants. We observed 5-fold higher serum levels of HMGB1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB1 stimulation increased the expression of TLR4 on CD14+-monocytes compared with unstimulated cells in the AH patients. The TNF-α and IL-1β production in response to HMGB1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB1 in their blood. This combined with an increased TLR4 expression, but an unaffected cytokine response to HMGB1 suggest that HMGB1 is not the primary driver of inflammation in AH.

KW - Journal Article

U2 - 10.1111/apm.12568

DO - 10.1111/apm.12568

M3 - Journal article

C2 - 27357188

VL - 124

SP - 741

EP - 747

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - 9

ER -