Thursday, May 16, 2013
Figure 1. Proposed model of Eritoran-mediated protection in influenza
infection. Oxidized phospholipids, produced in response to viral infection, are
proposed to bind to CD14 before being
transferred to lymphocyte antigen 96
(LY96; MD2). The lipid-MD2
complex interacts with toll-like receptor 4
(TLR4), resulting in
receptor dimerization and activation.
1 receptor domain containing adaptor protein (TIRAP),
receptor adaptor molecule 2
differentiation primary response gene 88 (MYD88)
and TICAM1 (TRIF)-are
then recruited, and the signal is transmitted inside the cell. TLR4 signaling
that occurs through MYD88 activates NF-kB
to induce production of proinflammatory cytokines, whereas TLR4 signaling that
occurs through TRIF activates interferon
regulatory factor 3 (IRF3)
to induce production of type I interferons.
the signaling pathway at which Eritoran may block influenza virus-induced
inflammation are indicated in red.
group speculates that Eritoran can inhibit interactions of oxidized
phospholipids with either CD14 or MD2, thus diminishing TLR4 signaling and
production of cytokines. This would blunt the effect of cytokines on reactive oxygen species (ROS)
generation and therefore limit the production of oxidized phospholipids.
(Figure based on Figure 8 in ref. 1.)