lipopolysaccharide-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by the binding of a lipopolysaccharide (LPS) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Lipopolysaccharides are major components of the outer membrane of Gram-negative bacteria, making them prime targets for recognition by the immune system. [GOC:mah, GOC:signaling, PMID:15379975]

Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, is a potent immunostimulant that triggers a complex signaling cascade known as the LPS-mediated signaling pathway. This pathway plays a crucial role in the host's innate immune response to bacterial infection. Upon entry into the host, LPS is recognized by a pattern recognition receptor called Toll-like receptor 4 (TLR4), which is expressed on the surface of immune cells like macrophages, dendritic cells, and neutrophils. TLR4, in conjunction with accessory proteins like myeloid differentiation factor 2 (MD2) and CD14, forms a complex that binds to LPS. This binding event initiates a cascade of intracellular signaling events that ultimately lead to the activation of transcription factors, such as nuclear factor kappa B (NF-κB), and the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The activation of NF-κB triggers the expression of a wide range of genes involved in inflammation, including those encoding cytokines, chemokines, and adhesion molecules. These pro-inflammatory mediators contribute to the recruitment and activation of immune cells at the site of infection, leading to the clearance of the invading bacteria. In addition to NF-κB activation, LPS signaling also activates other intracellular pathways, such as the mitogen-activated protein kinase (MAPK) cascade. The MAPK pathway regulates various cellular processes, including cell proliferation, differentiation, and apoptosis. LPS-mediated activation of MAPK pathways contributes to the inflammatory response by promoting the production of pro-inflammatory cytokines and the induction of cell death in infected cells. The LPS-mediated signaling pathway is tightly regulated to prevent excessive inflammation and tissue damage. Negative regulatory mechanisms, such as the induction of anti-inflammatory cytokines, the activation of inhibitory proteins, and the degradation of signaling components, are involved in limiting the duration and intensity of the inflammatory response. In summary, the LPS-mediated signaling pathway is a critical component of the innate immune response to bacterial infection. It involves the recognition of LPS by TLR4, the activation of downstream signaling pathways, the production of pro-inflammatory cytokines, and the recruitment and activation of immune cells. This pathway is tightly regulated to ensure an appropriate inflammatory response and minimize collateral damage to the host.'
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Proteins (20)

Compounds (582)