Anti-inflammatory activities of Reynoutria elliptica through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways

Reynoutria elliptica has been used in traditional Korean medicine to promote blood circulation, relieve pain, increase dieresis, and alleviate respiratory problems, through as yet undefined mechanisms. We set out to determine whether the anti-inflammatory effects of this plant are linked with its ability to suppress mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We found for the first time that the hexane fraction of Reynoutria elliptica (HRE) significantly inhibited LPS-stimulated NO and PGE2 synthesis. This is due to the diminishing of the mRNA and protein expression of iNOS and COX-2, respectively. HRE also suppressed LPS-stimulated TNF-α secretion in a dose-dependent manner, which might be due to the suppression of LPS-induced MAPKs and NF-κB activation. Moreover, our HPLC data demonstrated that the major components of the HRE were bioactive compounds such as emodin-6-Glc, emodin, and physcion. Overall, our results indicate that Reynoutria elliptica could be provided as a potential candidate for anti-inflammation treatment.     

HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways

Objective  

This study was designed to determine whether inhibition of heat shock protein 90 (HSP90) reduces pro-inflammatory mediator production by decreasing the nuclear factor (NF)-κB and Akt signaling pathways in immune-stimulated macrophages.     

Sparassis crispa suppresses mast cell-mediated allergic inflammation: Role of calcium, mitogen-activated protein kinase and nuclear factor-κB

Allergic inflammatory disease such as food allergy, asthma and atopic dermatitis are increasing worldwide. In this study, we investigated the effect of water extract of Sparassis crispa (WESC) Fr. (Aphyllophoromycetideae) on mast cell-mediated allergic inflammation and the possible mechanisms of action. WESC inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. WESC decreased immunoglobulin?E (IgE)-mediated passive cutaneous anaphylaxis. Additionally, WESC reduced histamine release and intracellular calcium in human mast cells activated by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. WESC decreased PMA and A23187-stimulated expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, inlerleukin (IL)-6 and IL-1β. The inhibitory effect of WESC on pro-inflammatory cytokines was nuclear factor-κB, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase-dependent. Our results suggest potential therapeutic application of WESC in allergic inflammatory diseases.     

c-Jun N-terminal kinase binding domain–dependent phosphorylation of mitogen-activated protein kinase kinase 4 and mitogen-activated protein kinase kinase 7 and balancing cross-talk between c-Jun N-terminal kinase and extracellular signal-regulated kinase pathways in cortical neurons

The c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase (MAPK) activated by stress-signals and involved in many different diseases. Previous results proved the powerful effect of the cell permeable peptide inhibitor d-JNKI1 (d-retro-inverso form of c-Jun N-terminal kinase-inhibitor) against neuronal death in CNS diseases, but the precise features of this neuroprotection remain unclear. We here performed cell-free and in vitro experiments for a deeper characterization of d-JNKI1 features in physiological conditions.     

Anti-inflammatory activity of the extracts from Rodgersia podophylla leaves through activation of Nrf2/HO-1 pathway,and inhibition of NF-κB and MAPKs pathway in mouse macrophage cells

Inflammation Research - Recently, Rodgersia podophylla has been reported to exhibit anti-inflammatory activity. However, little is known about the potential mechanisms about its anti-inflammatory...     

Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways

Bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites, but several clinical trials and high concentration treatment have shown that bisphosphonates have side effects that include bone loss and damage to normal cells. The aim of this study was to elucidate the protective effect and the possible mechanism of activated protein C (APC) against bisphosphonate-induced cell damage using primary cultured human umbilical vein endothelial cells (HUVECs). HUVECs were treated with APC (10 μg/ml) for 1 h, and then treated with bisphosphonates including alendronate, zoledronate and pamidronate. Bisphosphonates induced cell death in HUVECs but the cell death was blocked by treatment with APC. Bisphosphonates markedly induced caspase-3 activaion, which was diminished in cells exposed to APC. Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-κB (NF-κB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Furthermore, APC highly induced the expression of the endothelial protein c receptor (EPCR) in HUVEC cells. In conclusion, the present study demonstrates that APC inhibits bisphosphonate-induced endothelial cell death via EPCR-induced inactivation of caspase-3 and NF-κB, and also suggests that APC has the potential to be a therapeutic drug in various vascular diseases induced by endothelial cell damage.     

TNF-α and TGF-β1 regulate Syndecan-4 expression in nucleus pulposus cells: role of the mitogen-activated protein kinase and NF-κB pathways

Syndecan-4 is emerging as an important player in cell interaction with the extracellular environment and has been shown to be involved in the progression of intervertebral disc degeneration. However, the mechanism of syndecan-4 regulation by TNF-α and the role of TGF-β1 in regulating syndecan-4 expression remain poorly understood in nucleus pulposus (NP) cells. The aim of this study was to investigate these mechanisms. We exposed NP cells to TNF-α and the gene, protein expression, and promoter activity levels of syndecan-4 were measured by qPCR, western blotting, and the luciferase reporter assay, respectively. The activation of the MAPK and NF-κB pathways was detected using western blot analysis. Syndecan-4 expression in rat NP cells was increased by TNF-α, but this was neither time nor dose dependent in response to TNF-α. ERK1/2, JNK, and NF-κB pathways were activated following TNF-α treatment. Treatment with ERK1/2 and NF-κB inhibitors decreased the up-regulation of syndecan-4 by TNF-α. However, JNK inhibition showed no effect on syndecan-4 expression induced by TNF-α. TNF-α mediated up-regulation of syndecan-4 was antagonized by TGF-β1. This study provided evidence for the differential regulation by MAPK and NF-κB pathways in the over-expression of syndecan-4 promoted by TNF-α in NP cells. Our results demonstrate that TGF-β1 exerts anabolic effects on intervertebral discs by inhibiting the expression of syndecan-4.     

Modulation of p53 by mitogen-activated protein kinase pathways and protein kinase C δ during avian reovirus S1133-induced apoptosis

ARV S1133 infection caused apoptosis in vivo and in vitro; however, the intracellular signaling pathways have not been fully delineated. We have previously demonstrated that ARV S1133 activates proapoptotic signaling from Src to p53, and further investigated how ARV S1133 modulates p53. We found that ARV S1133 forms syncytia and induces apoptosis in CEF, DF1 and Vero cells with different kinetics. Enhancement of p53 phosphorylation and DNA-binding capacity to bax and bad promoters was found in this study to increase bax and bad expression in ARV S1133-infected cells. ARV S1133 activates PKC δ and p38 and JNK/SAPK pathways, and inhibition of Ras, p38, JNK/SAPK and PKC δ works efficiently against apoptosis. Suppression of p38, JNK/SAPK and PKC δ selectively abolished ARV S1133-mediated p53 phosphorylation; moreover, inhibition of Src did not affect ARV S1133-induced p38 and JNK/SAPK activation, whereas blocking of Ras resulted in a reduction in the activities of p38 and JNK/SAPK.