Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo

Sahoko Hirano, R. S. Rees, S. L. Yancy, M. J. Welsh, D. G. Remick, T. Yamada, J. Hata, R. R. Gilmont

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Lung edema during sepsis is triggered by formation of gaps between endothelial cells followed by macrophage infiltration. Endothelial gap formation has been proposed to involve changes in the structure of the actin filament cytoskeleton. Heat shock protein 27 (HSP27) is believed to modulate actin filament dynamics or structure, in a manner dependent on its phosphorylation status. We hypothesized that HSP27 may play a role in endothelial gap formation, by affecting actin dependent events in endothelial cells. As there has been no report concerning HSP27 in lung edema in vivo, we examined induction and phosphorylation of HSP27 in lung following LPS injection, as a model of sepsis. In lung, HSP27 mainly localized in capillary endothelial cells of the alveolus, and in smooth muscle cells of pulmonary arteries. HSP27 became significantly more phosphorylated at 3 h after LPS treatment, while the distribution of HSP27 remained unchanged. Pre-treatment with anti-TNFα antibody, which has been shown to reduce lung injury, blocked increases in HSP27 phosphorylation at 3 h. HSP27 phosphorylation was also increased in cultured rat pulmonary arterial endothelial cells (RPAEC) by treatment with TNFα, LPS, or H2O2. This phosphorylation was blocked by pretreatment with SB203580, an inhibitor of the upstream kinase, p38 MAP kinase. Increased endothelial permeability caused by H2O 2 in vitro was also blocked by SB203580. The amount of actin associated with HSP27 was reduced after treatment with LPS, or H 2O2. In summary, HSP27 phosphorylation temporally correlated with LPS induced pathological endothelial cell gap formation in vivo and in a cell culture model system. This is the first report of increased HSP27 phosphorylation associated with pathological lung injury in an animal model of sepsis.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalCell Biology and Toxicology
Volume20
Issue number1
DOIs
Publication statusPublished - 2004 Feb

Fingerprint

HSP27 Heat-Shock Proteins
Phosphorylation
Endothelial cells
Endothelial Cells
Actins
Lung
Actin Cytoskeleton
Sepsis
Lung Injury
Edema
Macrophages
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Therapeutics
Cell culture
Infiltration
Pulmonary Artery
Smooth Muscle Myocytes
Muscle
Rats

Keywords

  • Endothelial cells
  • Heart
  • Hydrogen peroxide
  • LPS
  • Lung injury
  • TNFα

ASJC Scopus subject areas

  • Cell Biology
  • Toxicology

Cite this

Hirano, S., Rees, R. S., Yancy, S. L., Welsh, M. J., Remick, D. G., Yamada, T., ... Gilmont, R. R. (2004). Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo. Cell Biology and Toxicology, 20(1), 1-14. https://doi.org/10.1023/B:CBTO.0000021019.50889.aa

Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo. / Hirano, Sahoko; Rees, R. S.; Yancy, S. L.; Welsh, M. J.; Remick, D. G.; Yamada, T.; Hata, J.; Gilmont, R. R.

In: Cell Biology and Toxicology, Vol. 20, No. 1, 02.2004, p. 1-14.

Research output: Contribution to journalArticle

Hirano, S, Rees, RS, Yancy, SL, Welsh, MJ, Remick, DG, Yamada, T, Hata, J & Gilmont, RR 2004, 'Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo', Cell Biology and Toxicology, vol. 20, no. 1, pp. 1-14. https://doi.org/10.1023/B:CBTO.0000021019.50889.aa
Hirano, Sahoko ; Rees, R. S. ; Yancy, S. L. ; Welsh, M. J. ; Remick, D. G. ; Yamada, T. ; Hata, J. ; Gilmont, R. R. / Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo. In: Cell Biology and Toxicology. 2004 ; Vol. 20, No. 1. pp. 1-14.
@article{8faba1d8c8714e489450b30ce05e574c,
title = "Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo",
abstract = "Lung edema during sepsis is triggered by formation of gaps between endothelial cells followed by macrophage infiltration. Endothelial gap formation has been proposed to involve changes in the structure of the actin filament cytoskeleton. Heat shock protein 27 (HSP27) is believed to modulate actin filament dynamics or structure, in a manner dependent on its phosphorylation status. We hypothesized that HSP27 may play a role in endothelial gap formation, by affecting actin dependent events in endothelial cells. As there has been no report concerning HSP27 in lung edema in vivo, we examined induction and phosphorylation of HSP27 in lung following LPS injection, as a model of sepsis. In lung, HSP27 mainly localized in capillary endothelial cells of the alveolus, and in smooth muscle cells of pulmonary arteries. HSP27 became significantly more phosphorylated at 3 h after LPS treatment, while the distribution of HSP27 remained unchanged. Pre-treatment with anti-TNFα antibody, which has been shown to reduce lung injury, blocked increases in HSP27 phosphorylation at 3 h. HSP27 phosphorylation was also increased in cultured rat pulmonary arterial endothelial cells (RPAEC) by treatment with TNFα, LPS, or H2O2. This phosphorylation was blocked by pretreatment with SB203580, an inhibitor of the upstream kinase, p38 MAP kinase. Increased endothelial permeability caused by H2O 2 in vitro was also blocked by SB203580. The amount of actin associated with HSP27 was reduced after treatment with LPS, or H 2O2. In summary, HSP27 phosphorylation temporally correlated with LPS induced pathological endothelial cell gap formation in vivo and in a cell culture model system. This is the first report of increased HSP27 phosphorylation associated with pathological lung injury in an animal model of sepsis.",
keywords = "Endothelial cells, Heart, Hydrogen peroxide, LPS, Lung injury, TNFα",
author = "Sahoko Hirano and Rees, {R. S.} and Yancy, {S. L.} and Welsh, {M. J.} and Remick, {D. G.} and T. Yamada and J. Hata and Gilmont, {R. R.}",
year = "2004",
month = "2",
doi = "10.1023/B:CBTO.0000021019.50889.aa",
language = "English",
volume = "20",
pages = "1--14",
journal = "Cell Biology and Toxicology",
issn = "0742-2091",
publisher = "Springer Netherlands",
number = "1",

}

TY - JOUR

T1 - Endothelial barrier dysfunction caused by LPS correlates with phosphorylation of HSP27 in vivo

AU - Hirano, Sahoko

AU - Rees, R. S.

AU - Yancy, S. L.

AU - Welsh, M. J.

AU - Remick, D. G.

AU - Yamada, T.

AU - Hata, J.

AU - Gilmont, R. R.

PY - 2004/2

Y1 - 2004/2

N2 - Lung edema during sepsis is triggered by formation of gaps between endothelial cells followed by macrophage infiltration. Endothelial gap formation has been proposed to involve changes in the structure of the actin filament cytoskeleton. Heat shock protein 27 (HSP27) is believed to modulate actin filament dynamics or structure, in a manner dependent on its phosphorylation status. We hypothesized that HSP27 may play a role in endothelial gap formation, by affecting actin dependent events in endothelial cells. As there has been no report concerning HSP27 in lung edema in vivo, we examined induction and phosphorylation of HSP27 in lung following LPS injection, as a model of sepsis. In lung, HSP27 mainly localized in capillary endothelial cells of the alveolus, and in smooth muscle cells of pulmonary arteries. HSP27 became significantly more phosphorylated at 3 h after LPS treatment, while the distribution of HSP27 remained unchanged. Pre-treatment with anti-TNFα antibody, which has been shown to reduce lung injury, blocked increases in HSP27 phosphorylation at 3 h. HSP27 phosphorylation was also increased in cultured rat pulmonary arterial endothelial cells (RPAEC) by treatment with TNFα, LPS, or H2O2. This phosphorylation was blocked by pretreatment with SB203580, an inhibitor of the upstream kinase, p38 MAP kinase. Increased endothelial permeability caused by H2O 2 in vitro was also blocked by SB203580. The amount of actin associated with HSP27 was reduced after treatment with LPS, or H 2O2. In summary, HSP27 phosphorylation temporally correlated with LPS induced pathological endothelial cell gap formation in vivo and in a cell culture model system. This is the first report of increased HSP27 phosphorylation associated with pathological lung injury in an animal model of sepsis.

AB - Lung edema during sepsis is triggered by formation of gaps between endothelial cells followed by macrophage infiltration. Endothelial gap formation has been proposed to involve changes in the structure of the actin filament cytoskeleton. Heat shock protein 27 (HSP27) is believed to modulate actin filament dynamics or structure, in a manner dependent on its phosphorylation status. We hypothesized that HSP27 may play a role in endothelial gap formation, by affecting actin dependent events in endothelial cells. As there has been no report concerning HSP27 in lung edema in vivo, we examined induction and phosphorylation of HSP27 in lung following LPS injection, as a model of sepsis. In lung, HSP27 mainly localized in capillary endothelial cells of the alveolus, and in smooth muscle cells of pulmonary arteries. HSP27 became significantly more phosphorylated at 3 h after LPS treatment, while the distribution of HSP27 remained unchanged. Pre-treatment with anti-TNFα antibody, which has been shown to reduce lung injury, blocked increases in HSP27 phosphorylation at 3 h. HSP27 phosphorylation was also increased in cultured rat pulmonary arterial endothelial cells (RPAEC) by treatment with TNFα, LPS, or H2O2. This phosphorylation was blocked by pretreatment with SB203580, an inhibitor of the upstream kinase, p38 MAP kinase. Increased endothelial permeability caused by H2O 2 in vitro was also blocked by SB203580. The amount of actin associated with HSP27 was reduced after treatment with LPS, or H 2O2. In summary, HSP27 phosphorylation temporally correlated with LPS induced pathological endothelial cell gap formation in vivo and in a cell culture model system. This is the first report of increased HSP27 phosphorylation associated with pathological lung injury in an animal model of sepsis.

KW - Endothelial cells

KW - Heart

KW - Hydrogen peroxide

KW - LPS

KW - Lung injury

KW - TNFα

UR - http://www.scopus.com/inward/record.url?scp=1842661193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842661193&partnerID=8YFLogxK

U2 - 10.1023/B:CBTO.0000021019.50889.aa

DO - 10.1023/B:CBTO.0000021019.50889.aa

M3 - Article

VL - 20

SP - 1

EP - 14

JO - Cell Biology and Toxicology

JF - Cell Biology and Toxicology

SN - 0742-2091

IS - 1

ER -