title: VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa.
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.
authors.affiliation: Immunotherapy Research Center, Korea Research of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Piao
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Mira
authors.initials: M
authors.lastname: Jeong
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Hu-Nan
authors.initials: HN
authors.lastname: Sun
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Suh
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D010529:Peritoneal Cavity / Q000382:microbiology / Q000473:pathology; D010538:Peritonitis / Q000382:microbiology / Q000503:physiopathology*; D010587:Phagocytosis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011552:Pseudomonas Infections / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000302:isolation & purification; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; D013879:Thioredoxins; C445672:Txnip protein, mouse