Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability

Yung Chun Chuang, Huan Yao Lei, Hsiao-Sheng Liu, Yee-Shin Lin, Tzu-Fun Fu, Trai-Ming Yeh

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Dengue virus (DENV) infection can cause mild dengue fever or severe dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Serum levels of the macrophage migration inhibitory factor (MIF) have been shown to be correlated with severity and mortality in DENV patients, but the pathogenic roles of MIF in DHF/DSS are still unclear. Increase in vascular permeability is an important hallmark of DHF/DSS. In this study, we found that DENV infection of the human hepatoma cell line (Huh 7) induced MIF production. Conditioned medium collected from DENV-infected Huh 7 cells enhanced the permeability of the human endothelial cell line (HMEC-1) which was reduced in the presence of a MIF inhibitor, ISO-1 or medium from DENV-infected MIF knockdown Huh 7 cells. To further identify whether MIF can alter vascular permeability, we cloned and expressed both human and murine recombinant MIF (rMIF) and tested their effects on vascular permeability both in vitro and in vivo. Indirect immunofluorescent staining showed that the tight junction protein ZO-1 of HMEC-1 was disarrayed in the presence of rMIF and partially recovered when cells were treated with ISO-1 or PI3K/MEK-ERK/JNK signaling pathway inhibitors such as Ly294002, U0126, and SP600215. In addition, ZO-1 disarray induced by MIF was also recovered when CD74 or CXCR2/4 expression of HMEC-1 were inhibited. Last but not least, the vascular permeabilities of the peritoneal cavity and dorsal cutaneous capillary were also increased in mice treated with rMIF. Taken together; these results suggest that MIF induced by DENV infection may contribute to the increase of vascular permeability during DHF/DSS. Therapeutic intervention of MIF by its inhibitor or neutralizing antibodies may prevent DENV-induced lethality.

Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalCytokine
Volume54
Issue number2
DOIs
Publication statusPublished - 2011 May 1

Fingerprint

Macrophage Migration-Inhibitory Factors
Dengue Virus
Capillary Permeability
Virus Diseases
Viruses
Severe Dengue
Dengue
Hemorrhage
Zonula Occludens-1 Protein
Cell Line
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Endothelial cells
Peritoneal Cavity
Conditioned Culture Medium
Neutralizing Antibodies
Phosphatidylinositol 3-Kinases
Hepatocellular Carcinoma
Permeability
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

@article{62f7db0920434680a43a5ace30961575,
title = "Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability",
abstract = "Dengue virus (DENV) infection can cause mild dengue fever or severe dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Serum levels of the macrophage migration inhibitory factor (MIF) have been shown to be correlated with severity and mortality in DENV patients, but the pathogenic roles of MIF in DHF/DSS are still unclear. Increase in vascular permeability is an important hallmark of DHF/DSS. In this study, we found that DENV infection of the human hepatoma cell line (Huh 7) induced MIF production. Conditioned medium collected from DENV-infected Huh 7 cells enhanced the permeability of the human endothelial cell line (HMEC-1) which was reduced in the presence of a MIF inhibitor, ISO-1 or medium from DENV-infected MIF knockdown Huh 7 cells. To further identify whether MIF can alter vascular permeability, we cloned and expressed both human and murine recombinant MIF (rMIF) and tested their effects on vascular permeability both in vitro and in vivo. Indirect immunofluorescent staining showed that the tight junction protein ZO-1 of HMEC-1 was disarrayed in the presence of rMIF and partially recovered when cells were treated with ISO-1 or PI3K/MEK-ERK/JNK signaling pathway inhibitors such as Ly294002, U0126, and SP600215. In addition, ZO-1 disarray induced by MIF was also recovered when CD74 or CXCR2/4 expression of HMEC-1 were inhibited. Last but not least, the vascular permeabilities of the peritoneal cavity and dorsal cutaneous capillary were also increased in mice treated with rMIF. Taken together; these results suggest that MIF induced by DENV infection may contribute to the increase of vascular permeability during DHF/DSS. Therapeutic intervention of MIF by its inhibitor or neutralizing antibodies may prevent DENV-induced lethality.",
author = "Chuang, {Yung Chun} and Lei, {Huan Yao} and Hsiao-Sheng Liu and Yee-Shin Lin and Tzu-Fun Fu and Trai-Ming Yeh",
year = "2011",
month = "5",
day = "1",
doi = "10.1016/j.cyto.2011.01.013",
language = "English",
volume = "54",
pages = "222--231",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "2",

}

Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability. / Chuang, Yung Chun; Lei, Huan Yao; Liu, Hsiao-Sheng; Lin, Yee-Shin; Fu, Tzu-Fun; Yeh, Trai-Ming.

In: Cytokine, Vol. 54, No. 2, 01.05.2011, p. 222-231.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability

AU - Chuang, Yung Chun

AU - Lei, Huan Yao

AU - Liu, Hsiao-Sheng

AU - Lin, Yee-Shin

AU - Fu, Tzu-Fun

AU - Yeh, Trai-Ming

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Dengue virus (DENV) infection can cause mild dengue fever or severe dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Serum levels of the macrophage migration inhibitory factor (MIF) have been shown to be correlated with severity and mortality in DENV patients, but the pathogenic roles of MIF in DHF/DSS are still unclear. Increase in vascular permeability is an important hallmark of DHF/DSS. In this study, we found that DENV infection of the human hepatoma cell line (Huh 7) induced MIF production. Conditioned medium collected from DENV-infected Huh 7 cells enhanced the permeability of the human endothelial cell line (HMEC-1) which was reduced in the presence of a MIF inhibitor, ISO-1 or medium from DENV-infected MIF knockdown Huh 7 cells. To further identify whether MIF can alter vascular permeability, we cloned and expressed both human and murine recombinant MIF (rMIF) and tested their effects on vascular permeability both in vitro and in vivo. Indirect immunofluorescent staining showed that the tight junction protein ZO-1 of HMEC-1 was disarrayed in the presence of rMIF and partially recovered when cells were treated with ISO-1 or PI3K/MEK-ERK/JNK signaling pathway inhibitors such as Ly294002, U0126, and SP600215. In addition, ZO-1 disarray induced by MIF was also recovered when CD74 or CXCR2/4 expression of HMEC-1 were inhibited. Last but not least, the vascular permeabilities of the peritoneal cavity and dorsal cutaneous capillary were also increased in mice treated with rMIF. Taken together; these results suggest that MIF induced by DENV infection may contribute to the increase of vascular permeability during DHF/DSS. Therapeutic intervention of MIF by its inhibitor or neutralizing antibodies may prevent DENV-induced lethality.

AB - Dengue virus (DENV) infection can cause mild dengue fever or severe dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Serum levels of the macrophage migration inhibitory factor (MIF) have been shown to be correlated with severity and mortality in DENV patients, but the pathogenic roles of MIF in DHF/DSS are still unclear. Increase in vascular permeability is an important hallmark of DHF/DSS. In this study, we found that DENV infection of the human hepatoma cell line (Huh 7) induced MIF production. Conditioned medium collected from DENV-infected Huh 7 cells enhanced the permeability of the human endothelial cell line (HMEC-1) which was reduced in the presence of a MIF inhibitor, ISO-1 or medium from DENV-infected MIF knockdown Huh 7 cells. To further identify whether MIF can alter vascular permeability, we cloned and expressed both human and murine recombinant MIF (rMIF) and tested their effects on vascular permeability both in vitro and in vivo. Indirect immunofluorescent staining showed that the tight junction protein ZO-1 of HMEC-1 was disarrayed in the presence of rMIF and partially recovered when cells were treated with ISO-1 or PI3K/MEK-ERK/JNK signaling pathway inhibitors such as Ly294002, U0126, and SP600215. In addition, ZO-1 disarray induced by MIF was also recovered when CD74 or CXCR2/4 expression of HMEC-1 were inhibited. Last but not least, the vascular permeabilities of the peritoneal cavity and dorsal cutaneous capillary were also increased in mice treated with rMIF. Taken together; these results suggest that MIF induced by DENV infection may contribute to the increase of vascular permeability during DHF/DSS. Therapeutic intervention of MIF by its inhibitor or neutralizing antibodies may prevent DENV-induced lethality.

UR - http://www.scopus.com/inward/record.url?scp=79953036625&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953036625&partnerID=8YFLogxK

U2 - 10.1016/j.cyto.2011.01.013

DO - 10.1016/j.cyto.2011.01.013

M3 - Article

VL - 54

SP - 222

EP - 231

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 2

ER -