PMID:11588035

Citation	Carballo, E and Blackshear, PJ (2001) Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome. Blood 98:2389-95
Abstract	Tristetraprolin (TTP) is a member of the CCCH tandem zinc-finger class of proteins. It can bind to and destabilize mRNAs encoding tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, mice deficient in TTP develop a complex syndrome characterized by cachexia, myeloid hyperplasia, and joint and skin inflammation. Studies using anti-TNF-alpha neutralizing antibodies demonstrated that this syndrome, at least in part, is a consequence of the excess production of TNF-alpha in the absence of TTP. To evaluate the role played by each TNF-alpha receptor in the pathogenesis of this syndrome, mice were generated that were deficient in TTP and either or both of the known TNF-alpha receptors (TNFRs), type 1 (TNFR1) and type 2 (TNFR2). Mice deficient in TTP and TNFR1, or in TTP and both receptors, were protected from developing the TNF-alpha-induced cachexia and inflammation. In contrast, mice deficient in TNFR2 were more severely affected than mice deficient in TTP alone, suggesting that TNFR2 might play a protective role in the development of the syndrome. In cultured cells derived from these mice, apparent cooperation between the TNFRs was required to achieve normal TNF-alpha-induced expression of TTP, TNF-alpha, and GM-CSF mRNAs. Finally, the results showed that TNFR1 plays an important role in mediating TNF-alpha-induced changes in TNF-alpha and GM-CSF mRNA stability.
Links	PubMed
Keywords	Animals; Antigens, CD/genetics; Antigens, CD/physiology; Bone Marrow Cells/cytology; Cells, Cultured; DNA-Binding Proteins; Gene Expression Regulation; Heterozygote Detection; Humans; Immediate-Early Proteins/deficiency; Immediate-Early Proteins/genetics; Immediate-Early Proteins/physiology; Macrophages/cytology; Mice; Mice, Knockout; RNA, Messenger/genetics; Receptors, Tumor Necrosis Factor/classification; Receptors, Tumor Necrosis Factor/deficiency; Receptors, Tumor Necrosis Factor/genetics; Receptors, Tumor Necrosis Factor/physiology; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Syndrome; Transcription, Genetic; Tristetraprolin; Tumor Necrosis Factor-alpha/genetics; Zinc Fingers
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