Interleukin-32β propagates vascular inflammation and exacerbates sepsis in a mouse model

Hanako Kobayashi, Jianhua Huang, Fei Ye, Yu Shyr, Timothy S. Blackwell, P. Charles Lin

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Inflammation is associated with most diseases, which makes understanding the mechanisms of inflammation vitally important. Methodology/Principal Findings: Here, we demonstrate a critical function of interleukin-32β (IL-32β) in vascular inflammation. IL-32β is present in tissues from humans, but is absent in rodents. We found that the gene is highly expressed in endothelial cells. Three isoforms of IL-32, named IL-32α, β, and ε, were cloned from human endothelial cells, with IL-32β being the major isoform. Pro-inflammatory cytokines (TNFα and IL-1β) induced IL-32β expression through NF-κB. Conversely, IL-32β propagated vascular inflammation via induction of vascular cell adhesion molecules and inflammatory cytokines. Accordingly, IL-32β increased adhesion of inflammatory cells to activated endothelial cells, a paramount process in inflammation. These results illustrate a positive feedback regulation that intensifies and prolongs inflammation. Importantly, endothelial/hematopoietic expression of IL-32β in transgenic mice elevated inflammation and worsened sepsis. This was demonstrated by significant elevation of leukocyte infiltration and serum levels of TNFα and IL-1β, increased vascular permeability and lung damage, and accelerated animal death. Together, our results reveal an important function of IL-32 in vascular inflammation and sepsis development. Conclusions/Significance: Our results reveal an important function of IL-32 in vascular inflammation and sepsis development.

Original languageEnglish
Article numbere9458
JournalPloS one
Volume5
Issue number3
DOIs
Publication statusPublished - 2010 Mar 5

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Interleukins
interleukins
blood vessels
Blood Vessels
Sepsis
inflammation
animal models
Inflammation
Endothelial cells
endothelial cells
Endothelial Cells
interleukin-1
Interleukin-1
Protein Isoforms
cytokines
Cytokines
Vascular Cell Adhesion Molecule-1
Capillary Permeability
Infiltration
cell adhesion

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kobayashi, Hanako ; Huang, Jianhua ; Ye, Fei ; Shyr, Yu ; Blackwell, Timothy S. ; Lin, P. Charles. / Interleukin-32β propagates vascular inflammation and exacerbates sepsis in a mouse model. In: PloS one. 2010 ; Vol. 5, No. 3.
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Interleukin-32β propagates vascular inflammation and exacerbates sepsis in a mouse model. / Kobayashi, Hanako; Huang, Jianhua; Ye, Fei; Shyr, Yu; Blackwell, Timothy S.; Lin, P. Charles.

In: PloS one, Vol. 5, No. 3, e9458, 05.03.2010.

Research output: Contribution to journalArticle

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