Prion protein participates in the protection of mice from lipopolysaccharide infection by regulating the inflammatory process.
Despite the overwhelming evidence of the involvement of prion protein (PrP) in prion disease pathogenesis, the normal functions of this cell surface glycoprotein remain unclear. Previously, we showed that PrP may have a dual regulatory role by regulating the opposite poles of pro-inflammation and anti-inflammation as well as tissue repair in activated microglia. In the present work, we compared the mRNA expression of inflammation-related cytokines (TNF-α, IL-1β, IL-6, NOS2, and IL-10) and IL-4-related alternative activation markers (Arg1 and Mrc1) after lipopolysaccharide (LPS) challenge in the brain and spleen and examined peripheral leukocyte recovery and LPS-induced mortality in PrP knockout mice (PrP(-/-)) and wild-type (WT) mice. During the acute phase, WT mice exhibited higher levels of pro-inflammatory cytokines in the brain and spleen than in PrP(-/-) mice, while PrP(-/-) mice sustained higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, Arg1, and Mrc1 during the later phase. PrP(-/-) mice also exhibited a slower peripheral leukocyte recovery process and higher mortality in response to LPS-induced septic shock. These results suggest that the PrP may participate in the protection of mice from LPS infection by regulating the process of inflammatory response.
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Jin
J
Liu
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Deming
D
Zhao
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Chunfa
C
Liu
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Tianjian
T
Ding
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Lifeng
L
Yang
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Xiaomin
X
Yin
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. zhouxm@cau.edu.cn.
Xiangmei
X
Zhou
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D011328:Prions; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C544448:Arg1 protein, mouse; D001119:Arginase