1. VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa
- Author
-
Piao, Zheng-Hao, Kim, Mi Sun, Jeong, Mira, Yun, Sohyun, Lee, Suk Hyung, Sun, Hu-Nan, Song, Hae Young, Suh, Hyun-Woo, Jung, Haiyoung, Yoon, Suk Ran, Kim, Tae-Don, Lee, Young-Ho, and Choi, Inpyo
- Subjects
- *
CHOLECALCIFEROL , *SEPTIC shock , *LABORATORY mice , *PSEUDOMONAS aeruginosa infections , *HEAT shock proteins , *REACTIVE oxygen species - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF