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The pathophysiological processes of inflammation can lead to a host of diseases, such as periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. The dysregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activation play important roles in the development of certain inflammatory diseases. Here, we investigated the effects of CDr10b which is originally developed for a microglia staining probe on inflammation, by modulating NF-κB activation and iNOS and COX-2 expression induced by lipopolysaccharide (LPS) in murine macrophages. The CDr10b suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. All the results suggest that CDr10b is a promising novel agent for the treatment of inflammatory diseases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-κB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense.

Inflammation is a pathological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).Aster yomenais used in traditional Korean remedies to treat cough, asthma, and insect bites. Here, we investigated the effects ofA. yomenaextract (EAY) on the expression of COX-2 and iNOS induced by LPS. EAY inhibited NF-κB activation and IκBα degradation induced by LPS. EAY suppressed LPS-induced COX-2 and iNOS expression which are the target genes regulated through NF-κB activation in macrophages. EAY also suppressed LPS-induced nitrite production. These results suggest that EAY has the potential to be developed as a potent anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

Inflammation is involved in numerous diseases including cancer. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play important roles in the development of certain inflammatory diseases.Eupatorium makinoi, which belongs to a family ofAsteraceaeplants, is used medicinally in East Asia. We investigated the effects of an ethanol extract ofE. makinoi(EEM) on nuclear factor-kappa B (NF-κB) activation and the expression of iNOS and COX-2 with lipopolysaccharide (TLR4 agonist) in murine macrophages. EEM suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. These results suggest that EEM may regulate TLR4 signalling pathways and this may be a useful strategy for anti-inflammatory therapies. [ABSTRACT FROM PUBLISHER]

Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-κB and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the MyD88- or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression. [ABSTRACT FROM AUTHOR]

Abstract: Toll-like receptors (TLRs) recognize molecular structures derived from microbes including bacteria, viruses, yeast, and fungi, and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of nuclear factor-κB (NF-κB) transcription factor leading to the induction of inflammatory gene products including cytokines and cyclooxygenase-2 (COX-2). In the present report, we demonstrate biochemical evidence that the fumaryl oxazolidinone derivative 4-Oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester (OSL07), which was previously synthesized in our laboratory, inhibits the NF-κB activation induced by TLR agonists and overexpression of downstream signaling components of TLRs, MyD88 and IKKβ. OSL07 also inhibits TLR agonist-induced COX-2 expression. These results indicate that the anti-inflammatory effects of OSL07 are caused by the modulation of the immune responses regulated by TLR signaling pathways. [Copyright &y& Elsevier]