TNFR2 expression on non-bone marrow-derived cells is crucial for lipopolysaccharide-induced septic shock and downregulation of soluble TNFR2 level in serum.
Persistently high serum levels of soluble tumor-necrosis factor (TNF) receptor 2 (sTNFR2) have been observed in septic shock and many inflammatory diseases. However, its origin and regulation during these pathological processes are still largely unknown. In this study, murine bone marrow (BM) chimeras selectively expressing TNFR2 on either BM-derived or non-BM-derived cells were generated and challenged with lipopolysaccharide (LPS). The results show that TNFR2 expression on non-BM-derived cells is crucial for both the sensitivity of mice to LPS and the downregulation of sTNFR2 in serum. Most importantly, sTNFR2 was released from both BM- and non-BM-derived cells. Non-BM TNFR1 expression influenced the sensitivity of mice to LPS challenge but not the level of serum sTNFR2. These results provide the first in vivo evidence for the origin and regulation of sTNFR2 in serum and could aid in the development of novel anti-TNF strategies against septic shock.
National Laboratory of Biomacromolecules, China-Japan Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Shubai
S
Liu
Lijie
L
Rong
Jingjing
J
Deng
Xiaopu
X
Zhao
Xiaoman
X
Liu
Xia
X
Xu
Zhihai
Z
Qin
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism*; D002678:Chimera; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012772:Shock, Septic / Q000097:blood*; D012995:Solubility / Q000187:drug effects
D008070:Lipopolysaccharides; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
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