VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa

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Title
VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa
Author(s)
Z H Piao; M S Kim; M Jeong; Sohyun Yun; S H Lee; H N Sun; Hae Young Song; Hyun Woo Suh; Haiyoung JungSuk Ran YoonTae-Don Kim; Y H Lee; In Pyo Choi
Bibliographic Citation
Cellular Immunology, vol. 280, no. 1, pp. 1-9
Publication Year
2012
Abstract
Vitamin-D3 upregulated protein-1 (VDUP1) is a stress response protein. Pseudomonas aeruginosa (P. aeruginosa) infection is a leading cause of death. Mice infected with live P. aeruginosa exhibit significantly decreased VDUP1 expression. However, the function of VDUP1 during P. aeruginosa-induced mouse bacteremic shock is unknown. To address the function of VDUP1 in P. aeruginosa-infected mice, we constructed a bacteremic shock model wherein both wild-type and VDUP1-deficient mice were infected intra-peritoneally with live P. aeruginosa. We found that VDUP1-deficient mice were more resistant to P. aeruginosa-induced bacteremic shock than wild-type mice, as shown by the increased survival, accelerated bacterial clearance and suppression of cytokine overproduction of the VDUP1-deficient mice. VDUP1 promoted the recruitment of neutrophils into the peritoneal cavities of infected mice. VDUP1 impeded the phagocytosis of non-opsonized P. aeruginosa via phosphatidylinositide 3-kinase (PI3K) pathway in macrophages. P. aeruginosa infection induced the generation of reactive oxygen species (ROS), and the increased production of ROS by the peritoneal cells of VDUP1-deficient mice was advantageous in clearing the bacteria. Overall, VDUP1 aggravates bacteremic shock; thus, VDUP1 can be considered a target molecule for the inhibition of P. aeruginosa-induced bacteremic shock.
Keyword
Bacteremic shockP. aeruginosaROSVDUP1
ISSN
0008-8749
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.cellimm.2012.11.003
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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