Disease relevance of Tlr3

• These perturbants include polyinosinic:polycytidylic acid (poly I:C, a ligand of toll-like receptor 3), agents that deplete regulatory T-cell (Treg) populations, and a non-beta-cell cytopathic parvovirus (Kilham rat virus [KRV]) [1].

High impact information on Tlr3

• Toll-like receptor 3 and STAT-1 contribute to double-stranded RNA+ interferon-gamma-induced apoptosis in primary pancreatic beta-cells [2].
• Treatment with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100% [3].
• Double-stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3-expressing astrocytes [4].
• Anti-TLR3 blocking antibody attenuated PIC upregulation of TNF-alpha mRNA and iNOS activity [4].
• Double-stranded RNA (dsRNA) is a byproduct of viral replication and serves as the signature molecule for viral infection via Toll-like receptor 3 (TLR3) largely restricted to circulating peripheral dendritic cells [4].

Biological context of Tlr3

• On the other hand, dsRNA plus IFN-gamma does not induce apoptosis in INS-1E cells, and expression of TLR3 and type I IFNs mRNAs is not detected in these cells [2].
• Using Western blot analysis and real-time qPCR, we determined that neonatal rat astrocyte cultures constitutively express TLR3 mRNA and protein, and that PIC dsRNA induced phosphorylation of eIF2alpha, as well as mRNA type I interferon (alpha/beta IFN)-response genes Mx1, PKR, and TLR3 [4].

Anatomical context of Tlr3

• Astrocyte TLR3 protein was downregulated after PIC treatment, however [4].

Analytical, diagnostic and therapeutic context of Tlr3

• We have previously observed by microarray analysis that PIC induces expression of several mRNAs encoding for genes downstream of Toll-like receptor 3 (TLR3) signaling pathway [2].

References