[Newcastle disease virus enhances tumoricidal activity of mouse NK cells against mouse Novikoff hepatoma cells via up-regulating expression of TRAIL on the NK cells].
OBJECTIVE
To observe the effect of intraperitoneal injection of Newcastle disease virus (NDV) on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression in mouse spleen NK cells and NK cells-mediated tumoricidal activity against mouse Novikoff hepatoma cell line, and explore the role of interferon (IFN)-γ in NDV-induced TRAIL expression and tumoricidal activity.


METHODS
NDV was injected intraperitoneally to BALB/c mice and IFN-γ receptor-deficient (IFN-γR-/-) B6.129S7 mice. Twelve hours after injection, the concentration of IFN-γ in peripheral blood from BALB/c mice was determined by ELISA. Mouse spleen NK cells were separated. The mRNA and protein expression of TRAIL in NK cells were detected through reverse transcription PCR (RT-PCR) and Western blotting. Lactate dehydrogenase (LDH) release assay was used to determine the cytotoxic activity of NK cells against mouse hepatoma cells.


RESULTS
NDV injection increased the IFN-γ concentration in peripheral blood of BALB/c mice, induced up-regulation of TRAIL at the mRNA and protein levels in mouse spleen NK cells, and enhanced the killing ability of mouse spleen NK cells towards Novikoff hepatoma cells. Blocking TRAIL by neutralizing antibody suppressed the cytotoxic activity of NK cells against Novikoff hepatoma cells. Furthermore, NDV injection in IFN-γR-/- B6.129S7 mice did not make significant difference from control group in TRAIL expression in spleen NK cells, and the tumoricidal activity of IFN-γR-/- B6.129S7 mouse spleen NK cells against Novikoff hepatoma cells was significantly lower than that of BALB/c mouse NK cells.


CONCLUSIONS
Intraperitoneal injection with NDV could enhance tumoricidal activity of mouse spleen NK cells in vitro, and one of the mechanisms might be that NDV injection up-regulates TRAIL expression in NK cells through the IFN-γ receptor pathway.
Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
Dezhi
D
Song
Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
Ying
Y
Liang
Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
Xiaohui
X
Fan
Department of Clinical Laboratory, First Affiliated Hospital, Guangxi University of Traditional Chinese Medicine, Nanning 530023, China.
Jun
J
Yin
Qingdao Center For Disease Control & Prevention, Qingdao 266033, China.
Jinling
J
Gong
Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
Zhenping
Z
Lai
Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China.
Lingxi
L
Gao
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D009522:Newcastle disease virus / Q000502:physiology*; D051381:Rats; D013154:Spleen / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D015854:Up-Regulation
D053221:TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma