scholarly journals Isopanduratin A Inhibits Tumor Necrosis Factor (TNF)-α-Induced Nuclear Factor κB Signaling Pathway by Promoting Extracellular Signal-Regulated Kinase-Dependent Ectodomain Shedding of TNF Receptor 1 in Human Lung Adenocarcinoma A549 Cells

BioChem ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 174-189
Author(s):  
Chihiro Moriwaki ◽  
Riho Tanigaki ◽  
Yasunobu Miyake ◽  
Nghia Trong Vo ◽  
Mai Thanh Thi Nguyen ◽  
...  
Keyword(s):  
Map Kinase ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
P38 Map Kinase ◽  
Ectodomain Shedding ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Lung Adenocarcinoma A549

Tumor necrosis factor α (TNF-α) induces the nuclear factor κB (NF-κB) signaling pathway via TNF receptor 1 (TNF-R1). We recently reported that isopanduratin A inhibited the TNF-α-induced NF-κB signaling pathway in human lung adenocarcinoma A549 cells. In the present study, we found that isopanduratin A did not inhibit the interleukin-1α-induced NF-κB signaling pathway in A549 cells. Isopanduratin A down-regulated the expression of TNF-R1 in these cells. We also revealed that isopanduratin A down-regulated the cell surface expression of TNF-R1 by promoting the cleavage of TNF-R1 into its soluble forms. TAPI-2, an inhibitor of TNF-α-converting enzyme, suppressed the inhibitory activity of isopanduratin A against the TNF-α-induced activation of NF-κB. The mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) kinase inhibitor U0126, but not the p38 MAP kinase inhibitor SB203580, blocked the ectodomain shedding of TNF-R1 induced by isopanduratin A. Consistent with this result, isopanduratin A induced the rapid phosphorylation of ERK, but not p38 MAP kinase. Isopanduratin A also promoted the phosphorylation of eukaryotic initiation factor 2α (eIF2α). The present results indicate that isopanduratin A inhibits TNF-α-induced NF-κB signaling pathway by promoting ERK-dependent ectodomain shedding of cell surface TNF-R1, and also decreases cellular TNF-R1 levels through the phosphorylation of eIF2α in A549 cells.

scholarly journals Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 107-121
Author(s):  
Nghia Trong Vo ◽  
Eiichi Kusagawa ◽  
Kaori Nakano ◽  
Chihiro Moriwaki ◽  
Yasunobu Miyake ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Lung Adenocarcinoma ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Lung Adenocarcinoma A549

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.

Hypertonicity activates MAP kinases and inhibits HCO 3 − absorption via distinct pathways in thick ascending limb

1998 ◽  
Vol 275 (4) ◽  
pp. F478-F486 ◽  
Author(s):  
Bruns A. Watts ◽  
John F. Di Mari ◽  
Roger J. Davis ◽  
David W. Good
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Kinase Inhibitor ◽  
Early Response ◽  
P38 Map Kinase ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Erk Activity

Mitogen-activated protein (MAP) kinases are activated by osmotic stress in a variety of cells, but their function and regulation in renal tubules is poorly understood. The present study was designed to examine the osmotic regulation of MAP kinases in the medullary thick ascending limb (MTAL) of the rat and to determine their possible role in the hyperosmotic inhibition of[Formula: see text] absorption in this segment. Tissues from the inner stripe of the outer medulla and microdissected MTALs were incubated at 37°C in control (290 mosmol/kgH2O) or hyperosmotic (300 mM added mannitol) solution for 15 min. Activities of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase were then measured using immune complex assays. Hyperosmolality increased p38 MAP kinase activity (2.3-fold) and ERK activity (2.0-fold) but had no effect on JNK activity (1.1-fold). Exposure to hyperosmolality for various times showed that the activation of p38 MAP kinase was rapid (≤5 min) and was sustained for up to 60 min, whereas the activation of ERK was transient (ERK activity peaked at 15 min, then declined to basal levels at 30 min). Pretreatment with the MAP kinase kinase inhibitor PD98059 (15 μM) blocked the hyperosmotic activation of p38 MAP kinase and ERK but did not prevent hyperosmotic inhibition of[Formula: see text] absorption. These results show that hyperosmolality differentially activates p38 MAP kinase and ERK in the MTAL. In contrast, we found no evidence for involvement of JNK in the early response to hyperosmotic stress. Eliminating the activation of p38 MAP kinase and ERK does not prevent hyperosmotic inhibition of [Formula: see text]absorption, suggesting that hyperosmolality inhibits apical membrane Na+/H+exchange (NHE3) activity via a signaling pathway distinct from these MAP kinase pathways.

TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway

2000 ◽  
Vol 292 (4) ◽  
pp. 180-187 ◽  
Author(s):  
R. Pfundt ◽  
M. Wingens ◽  
M. Bergers ◽  
M. Zweers ◽  
M. Frenken ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Human Keratinocytes ◽  
P38 Map Kinase ◽  
Tnf Α ◽  
Dependent Pathway

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H2O2 and PDGF in mesangial cells

2002 ◽  
Vol 282 (3) ◽  
pp. F485-F491 ◽  
Author(s):  
Misako Hayama ◽  
Risa Inoue ◽  
Satoshi Akiba ◽  
Takashi Sato
Keyword(s):  
Arachidonic Acid ◽  
Map Kinase ◽  
Mesangial Cells ◽  
P38 Map Kinase ◽  
Arachidonic Acid Release ◽  
Cytosolic Phospholipase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Acid Release ◽  
Map Kinase Pathways

Increased prostaglandin production is implicated in the pathogenesis of glomerular disease. With this consideration, we examined the combined effects of reactive oxygen species and platelet-derived growth factor (PDGF), which might initiate glomerular dysfunction, on arachidonic acid release and cytosolic phospholipase A2 (cPLA2) activation in rat mesangial cells. H2O2-induced release of arachidonic acid was enhanced by PDGF, which by itself had little effect on the release, and the enhancement was completely inhibited by a cPLA2 inhibitor. The phosphorylation of cPLA2, extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H2O2 or PDGF alone and except for ERK was enhanced further by the two in combination. The release of arachidonic acid induced by PDGF together with H2O2 was inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when the two inhibitors were combined; the inhibitory pattern was similar to that for the phosphorylation of cPLA2. These results suggest that the ERK and p38 MAP kinase pathways are involved in the increase in cPLA2activation and arachidonic acid release induced by PDGF together with H2O2.

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