Lipopolysaccharide signaling in endothelial cells

Abstract

Sepsis is the systemic immune response to severe bacterial infection. The innate immune recognition of bacterial and viral products is mediated by a family of transmembrane receptors known as Toll-like receptors (TLRs). In endothelial cells, exposure to lipopolysaccharide (LPS), a major cell wall constituent of Gramnegative bacteria, results in endothelial activation through a receptor complex consisting of TLR4, CD14 and MD2. Recruitment of the adaptor protein myeloid differentiation factor (MyD88) initiates an MyD88-dependent pathway that culminates in the early activation of nuclear factor-jB (NF-jB) and the mitogen-activated protein kinases. In parallel, a MyD88-independent pathway results in a late-phase activation of NF-jB. The outcome is the production of various proinflammatory mediators and ultimately cellular injury, leading to the various vascular sequelae of sepsis. This review will focus on the signaling pathways initiated by LPS binding to the TLR4 receptor in endothelial cells and the coordinated regulation of this pathway.

Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

“…To further suppress the multiplication of invading pathogens, the host system has been shown to initiate the processes of apoptosis through the binding of FADD (Fas-associated death domain protein) to the DD (death domain) of MyD88 and the recruitment of CASP8 [3,13,27]. The expression of NF-κB and IRF3 induced genes may cause changes in surrounding cells that enhance both innate and acquired responses to pathogenic ligands [27].…”

Increased expression and internalization of the endotoxin coreceptor CD14 in enterocytes occur as an early event in the development of experimental necrotizing enterocolitis

“…LPS-dependent TLR4 activation is known to involve a family of co-receptors including MD2 and CD14 (11). Although the exact nature of interaction between these molecules is not known, it is thought that LPS can be shuttled to MD2 by CD14, allowing for a direct interaction between LPS-bound MD2 and TLR4 (12,13). Whereas both CD14-dependent and CD14-indepent activation of TLR4 has been documented, it is unclear what role, if any CD14 may play in the development of experimental NEC (14)(15)(16).…”

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

“…LPS is known to signal via Toll-like receptor (TLR)-4, thus having pro-inflammatory properties. 42 Therefore, septic systemic inflammation caused by bacterial infection in patients with congenital CMV infection may enhance susceptibility of the inner ear to CMV infection, as in the inner ears of MCMV-infected mice stimulated by LPS. Furthermore, it has been reported that bacterial infection or administration of LPS triggers reactivation of latent pulmonary CMV in immunocompetent mice.…”

“…40 The receptors of the innate immune system are activated by microbial components such as LPS, which is a key molecule involved in the initiation of the sepsis syndrome. 41,42 Miller et al 43 proposed the hypothesis that the variability of bacterial ligands, such as LPS and their innate LPS induce MCMV-infected labyrinthitis L Li et al immune receptors, is an important factor in determining the outcome of infectious disease. There is a relationship between the clinical course of patients with septic shock and acute CMV infection.…”