Data di Pubblicazione:
2013
Citazione:
Role of TIR8/SIGIRR in regulating TLR and IL-1R like-dependent platelet activation / A. Anselmo, C. Soldani, S. Gentile, M. Bacci, A. Voza, M. Nebuloni, G.L. Mendolicchio, A. Mantovani, F. Riva, C. Garlanda - In: Immunitas Vis Naturae: BOOK OF ABSTRACTS of the 15th International Congress of Immunology[s.l] : The editors, 2013 Aug. - pp. 269 (( Intervento presentato al 15. convegno International Congress of Immunology tenutosi a Milano nel 2013.
Abstract:
TIR8, or single Ig IL-1R-related molecule, SIGIRR, is a member of the
IL-1R like (ILR) family, which acts as negative regulator of TLR and
ILR signalling, playing non-redundant roles in tuning inflammatory
responses in different pathological conditions.
Platelets express functional TLRs, which are involved in sepsisinduced
thrombocytopenia, binding of bacteria, neutrophil
extracellular trap production and platelet activation via P-selectin and
active GPaIIIbII upregulation. In addition, IL-1RI has been shown in
platelets.
We investigated the expression of TIR8/SIGIRR and other ILR
regulated by TIR8 in platelets, and defined the potential involvement
of TIR8/SIGIRR in TLR- and ILR-dependent platelet activation. We
confirmed IL-1RI expression and showed for the first time
TIR8/SIGIRR, IL-18R and IL-33R expression in human and murine
platelets and megakaryocytes. Functional studies showed that
stimulation with TLR and ILR ligands (LPS, IL-1βand IL-18) induced
upregulation of P-selectin and active GPIIbIIIa and calcium
mobilization. Platelet TIR8/SIGIRR expression was downregulated
upon LPS stimulation or in patients with Systemic Inflammatory
Response Syndrome compared to healthy donors. Finally, functional
studies showed that Tir8-deficiency in mice was associated to platelet
hyperactivity in basal conditions and upon stimulation with LPS, IL-18
and IL-1β, as demonstrated by increased P-selectin and active
GPaIIIbII upregulation, calcium mobilization and neutrophil/platelet
aggregation.
Thus, TIR8/SIGIRR is a regulator of platelet activation in inflammatory
conditions induced by TLR and ILR family ligands. The modulation of
TIR8/SIGIRR expression in platelets in severe inflammatory
conditions suggests that it might represent a novel diagnostic or
therapeutic target in prothrombotic conditions associated to
inflammatory diseases.
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
A. Anselmo, C. Soldani, S. Gentile, M. Bacci, A. Voza, M. Nebuloni, G.L. Mendolicchio, A. Mantovani, F. Riva, C. Garlanda
Link alla scheda completa:
Titolo del libro:
Immunitas Vis Naturae: BOOK OF ABSTRACTS of the 15th International Congress of Immunology