The pathogen-associated molecular pattern, polyinosinic-polycytidylic acid [poly(I:C)], and LPS were used to study type-I IFN and TNF responses in human macrophages. Additionally, activation of the key signaling pathways, IFN-regulatory factor 3 (IRF3) and NF-kappaB, were studied. We found that TNF production occurred rapidly after LPS stimulation.

2024年8月30日 · Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and …

In vitro experiments revealed that NLRP3 overexpression by adenovirus could offset protective effects of STING knockdown in LPS-induced cardiomyocytes. Additionally, LPS stimulation also promoted the production of intracellular reactive oxygen (ROS), which further induced the NLRP3 translocation to the cytoplasm from the nucleus.

2018年2月5日 · By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to switch-like responses to a viral...

2024年5月30日 · Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen...

2006年9月1日 · In addition to IRF3 and IRF7, induction of the nitric-oxide synthase 2 (Nos2) gene, an event that is crucial for antibacterial responses, depends on IRF1 in LPS- and IFNγ (type II...

2019年6月1日 · In wild type mice and cardiomyocytes, LPS stimulation triggered the perinuclear translocation of STING, which further bound to Type-I interferons (IFN) regulatory factor 3 (IRF3) and phosphorylated IRF3. Phosphorylated (P-) IRF3 subsequently translocated into nucleus and increased the expression of NOD-like receptor protein 3 (NLRP3).

TANK Is Involved in the LPS-mediated IRF3/7-activating Pathway—To demonstrate the existence of an endogenous, signal-responsive TANK-containing protein complex that phosphorylates IRF3/7, we first stimulated RAW 264.7 macrophages with LPS, which is known to activate TBK1-IKKϵ through the TLR4-dependent pathway (23, 41), or with TNFα and ...

2003年7月11日 · Using IRF-3 deficient mice, we show here that IRF-3 is indeed essential for the LPS-mediated IFN-beta gene induction. Loss of IRF-3 also affects the expression of profile of other cytokine/chemokine genes. We also provide evidence that the LPS/TLR4 signaling activates IRF-7 to induce IFN-beta, if IRF-7 is induced by IFNs prior to LPS simulation.

2003年7月11日 · In the present study, we used mice deficient in the IRF-3 gene (IRF-3 −/− mice) and determined how the loss of IRF-3 affects the LPS-induced gene induction events in the primary DCs in vitro and the LPS-induced endotoxin shock in the mutant mice. Our results provide genetic evidence that IRF-3 is indeed a molecule essential for the LPS/TLR ...