Available online 5 May 2022, 108198
AbstractAbnormal regulation of pro-inflammatory cytokine and chemokine mediators can contribute to the excess inflammation characteristic of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, Crohn's disease, type 1 diabetes, and many others. The tristetraprolin (TTP) family consists of a small group of related RNA-binding proteins that bind to preferred AU-rich binding sites within the 3′-untranslated regions of specific mRNAs to promote mRNA deadenylation and decay. TTP deficient mice develop a severe systemic inflammatory syndrome consisting of arthritis, myeloid hyperplasia, dermatitis, autoimmunity and cachexia, due at least in part to the to the excess accumulation of proinflammatory chemokine and cytokine mRNAs and their encoded proteins. To investigate the possibility that increased TTP expression or activity might have a beneficial effect on inflammatory diseases, at least two mouse models have been developed that provide proof of principle that increasing TTP activity can promote the decay of pro-inflammatory and other relevant transcripts, and decrease the severity of mouse models of inflammatory disease. Animal studies of this type are summarized here, and we briefly review the prospects for harnessing these insights for the development of TTP-based anti-inflammatory treatments in humans.
KeywordsRNA-binding protein
Tristetraprolin (TTP)
Zfp36
Cytokines
Inflammation
Tumor necrosis factor
AbbreviationsBMDMbone marrow-derived macrophages
3’-UTR3′-untranslated regions
MAPmitogen activated protein
NOT1 BDNOT1 binding domain
GM-CSFgranulocyte macrophage colony-stimulating factor
CAIAcollagen antibody-induced arthritis
H and Ehematoxylin and eosin
EAEexperimental autoimmune encephalitis
MOGmyelin oligodendrocyte glycoprotein
TRAPtartrate-resistant acid phosphate
EAUexperimental autoimmune uveitis
IRBPinterphotoreceptor retinoid-binding protein
BALFbronchoalveolar lavage fluid
HPCshematopoietic progenitor cells
DMBA7,12-dimethylbenz[a]anthracene
TPA12–0 tetradecanoylphorbol-13-acetate
SPEMspasmolytic polypeptide-expressing metaplasia
MAPKAPK2MAPK-activated protein kinase 2
COPDchronic obstructive pulmonary disease
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