Interleukin-32beta propagates vascular inflammation and exacerbates sepsis in a mouse model.
BACKGROUND
Inflammation is associated with most diseases, which makes understanding the mechanisms of inflammation vitally important.


RESULTS
Here, we demonstrate a critical function of interleukin-32beta (IL-32beta) in vascular inflammation. IL-32beta 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-32alpha, beta, and epsilon, were cloned from human endothelial cells, with IL-32beta being the major isoform. Pro-inflammatory cytokines (TNFalpha and IL-1beta) induced IL-32beta expression through NF-kappaB. Conversely, IL-32beta propagated vascular inflammation via induction of vascular cell adhesion molecules and inflammatory cytokines. Accordingly, IL-32beta 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-32beta in transgenic mice elevated inflammation and worsened sepsis. This was demonstrated by significant elevation of leukocyte infiltration and serum levels of TNFalpha and IL-1beta, 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
Our results reveal an important function of IL-32 in vascular inflammation and sepsis development.
Kobayashi
Hanako
H
Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Huang
Jianhua
J
Ye
Fei
F
Shyr
Yu
Y
Blackwell
Timothy S
TS
Lin
P Charles
PC
D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C496971:IL32 protein, human; D053583:Interleukin-1beta; D007378:Interleukins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha