PPARδ deficiency disrupts hypoxia-mediated tumorigenic potential of colon cancer cells.

Peroxisome proliferator-activated receptor (PPAR) δ is highly expressed in colon epithelial cells and closely linked to colon carcinogenesis. However, the role of PPARδ in colon cancer cells in a hypoxic tumor microenvironment is not fully understood. We found that expression of the tumor-promoting cytokines, IL-8 and VEGF, induced by hypoxia (<1% O2) and deferoxamine (a hypoxia mimetic) was significantly attenuated in PPARδ-deficient HCT116 colon cancer cells.

Suppression of Toll-like receptor 4 activation by endogenous oxidized phosphatidylcholine, KOdiA-PC by inhibiting LPS binding to MD2.

Objective: Activation of Toll-like receptor 4 (TLR4) triggers immune and inflammatory events by sensing endogenous danger signals as well as invading pathogens and contributes to the development of chronic inflammatory diseases. In this study, we investigated effect of 1-palmitoyl-2-(5-keto-6-octenedioyl)-sn-glycero-3-phosphocholine (KOdiA-PC), an oxidized phosphatidylcholine, on TLR4 activation and the underlying regulatory mechanism.

Methods: RAW264.

Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2.

Background And Purpose: Toll-like receptors (TLRs) play a crucial role in recognizing invading pathogens and endogenous danger signal to induce immune and inflammatory responses. Since dysregulation of TLRs enhances the risk of immune disorders and chronic inflammatory diseases, modulation of TLR activity by phytochemicals could be useful therapeutically. We investigated the effect of caffeic acid phenethyl ester (CAPE) on TLR-mediated inflammation and the underlying regulatory mechanism.

PI3K/Akt contributes to increased expression of Toll-like receptor 4 in macrophages exposed to hypoxic stress.

Toll-like receptors (TLRs) play critical roles in triggering immune and inflammatory responses by detecting invading microbial pathogens and endogenous danger signals. Increased expression of TLR4 is implicated in aggravated inflammatory symptoms in ischemic tissue injury and chronic diseases. Results from our previous study showed that TLR4 expression was upregulated by hypoxic stress mediated by hypoxia-inducible factor-1 (HIF-1) at a transcriptional level in macrophages.

Intrinsic and extrinsic regulation of innate immune receptors.

Pattern recognition receptors (PRRs) in innate immune cells play a pivotal role in the first line of host defense system. PRRs recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to initiate and regulate innate and adaptive immune responses. PRRs include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), which have their own features in ligand recognition and cellular location.

Alteration of Toll-like receptor 4 activation by 4-hydroxy-2-nonenal mediated by the suppression of receptor homodimerization.

Toll-like receptors (TLRs) detect invading microbial pathogens and initiate immune responses as part of host defense mechanisms. They also respond to host-derived substances released from injured cells and tissues to ensure wound healing and tissue homeostasis. Dysregulation of TLRs increases the risk of chronic inflammatory diseases and immune disorders.