Mini-TrpRS is essential for IFNγ-induced monocyte-derived giant cell formation.
Cytokine
; 142: 155486, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-33721618
ABSTRACT
Truncated tryptophanyl-tRNA synthetase (mini-TrpRS), like any other aminoacyl-tRNA synthetases, canonically functions as a protein synthesis enzyme. Here we provide evidence for an additional signaling role of mini-TrpRS in the formation of monocyte-derived multinuclear giant cells (MGCs). Interferon-gamma (IFNγ) readily induced monocyte aggregation leading to MGC formation with paralleled marked upregulation of mini-TrpRS. Small interfering (si)RNA, targeting mini-TrpRS in the presence of IFNγ prevented monocyte aggregation. Moreover, blockade of mini-TrpRS, either by siRNA, or the cognate amino acid and decoy substrate D-Tryptophan to prevent mini-TrpRS signaling, resulted in a marked reduction in expression of the purinergic receptor P2X 7 (P2RX7) in monocytes activated by IFNγ. Our findings identify mini-TrpRS as a critical signaling molecule in a mechanism by which IFNγ initiates monocyte-derived giant cell formation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tryptophan-tRNA Ligase
/
Monocytes
/
Giant Cells
/
Interferon-gamma
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cytokine
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2021
Document type:
Article