Mini-TrpRS is essential for IFNy-induced monocyte-derived giant cell formation

Biros, Erik, Vangaveti, Venkat, and Moran, Corey (2021) Mini-TrpRS is essential for IFNy-induced monocyte-derived giant cell formation. Cytokine, 142. p. 155486.

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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.

Item ID: 73163
Item Type: Article (Research - C1)
ISSN: 1096-0023
Keywords: Interferon-gamma, Tryptophanyl-tRNA synthetase, Purinergic receptor P2X 7, Multinucleated giant cells
Copyright Information: © 2021 Elsevier Ltd. All rights reserved
Date Deposited: 24 Mar 2022 03:33
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310103 Cell metabolism @ 50%
31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310105 Cellular interactions (incl. adhesion, matrix, cell wall) @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 20%
20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified @ 80%
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