scholarly journals Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7725 ◽  
Author(s):  
Toshiaki Ara ◽  
Masanori Koide ◽  
Hiroyuki Kitamura ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Diseases ◽  
Treated Mouse ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Mouse Macrophage ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Concentration Dependent Manner ◽  
Inflammatory Drugs

We previously reported that shokyo and kankyo, which are water-extracted fractions of ginger, reduced LPS-induced PGE2 production in human gingival fibroblasts. In this study, we examined the effects of these herbs on LPS-treated mouse macrophage RAW264.7 cells. Both shokyo and kankyo reduced LPS-induced PGE2 production in a concentration-dependent manner. Shokyo and kankyo did not inhibit cyclooxygenase (COX) activity, nor did they alter the expression of molecules in the arachidonic acid cascade. In addition, these herbs did not alter NF-κB p65 translocation into nucleus, or phosphorylation of p65 or ERK. These results suggest that shokyo and kankyo inhibit cPLA2 activity. Although 6-shogaol produced similar results to those of shokyo and kankyo, the concentration of 6-shogaol required for the reduction of PGE2 production were higher than those of 6-shogaol in shokyo and kankyo. Therefore, several gingerols and shogaols other than 6-shogaol may play a role in the reduction of LPS-induced PGE2 production. Thus, 6-shogaol, and other gingerols and shogaols inhibit cPLA2 activity and reduce LPS-induced PGE2 production via a different mechanism from traditional anti-inflammatory drugs. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for inflammatory diseases.

scholarly journals Effect of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

2017 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade

Previously, we revealed that several kampo medicines which are used for the patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] decreased prostaglandin (PG)E2 by LPS-treated human gingival fibroblasts (HGFs). Currently, we examined other kampo medicines which are used for the patients with deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs which construct shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently decreased LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly decreased and bakumondoto did not decrease PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activities and the expressions of molecules involved in arachidonic acid cascade. Next, we examined which herbs constructing shinbuto and ninjinto decrease LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo did not alter the expressions of molecules involved in arachidonic acid cascade. These results suggest that shokyo and kankyo suppress phospholipase (PL)A2 activity. We demonstrated that kampo medicines for the patients with deficiency pattern may suppress inflammatory responses in addition to those with excess and medium patterns. Moreover, kampo medicines which contain shokyo or kankyo are considered to be effective for the treatment of the inflammatory diseases.

scholarly journals Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

2017 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Cytosolic Phospholipase ◽  
Cox 2

Previously, we revealed that several kampo medicines that are used for patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] reduced prostaglandin (PG)E<2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

scholarly journals Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4120 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Cytosolic Phospholipase ◽  
Cox 2

Previously, we revealed that several kampo medicines used for patients with excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

scholarly journals Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

2017 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Cytosolic Phospholipase ◽  
Cox 2

Previously, we revealed that several kampo medicines that are used for patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] reduced prostaglandin (PG)E<2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

scholarly journals Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

2006 ◽  
Vol 85 (5) ◽  
pp. 452-456 ◽  
Author(s):  
M.M. Zavarella ◽  
O. Gbemi ◽  
J.D. Walters
Keyword(s):  
Steady State ◽  
Connective Tissue ◽  
Inflammatory Mediator ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Temperature Dependent ◽  
Tnf Α ◽  
Steady State Levels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 μg/mL and a Vmax of 1.42 ng/min/μg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-α. In humans, systemically administered naproxen attained steady-state levels of 61.9 μg/mL in blood and 9.4 μg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 μg/mL and 1.5 μg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

scholarly journals Signal regulatory protein α1 is involved in the inhibitory effect of glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell and mouse peritoneal macrophage

2008 ◽  
Vol 41 (5) ◽  
pp. 393-403 ◽  
Author(s):  
Xiaohui Wang ◽  
Yidong Li ◽  
Xiaoyan Zhu ◽  
Yan Wang ◽  
Fei Diao ◽  
...  
Keyword(s):  
Rna Interference ◽  
Peritoneal Macrophage ◽  
Inflammatory Responses ◽  
Regulatory Protein ◽  
Mouse Peritoneal Macrophage ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Proliferation Inhibition ◽  
Murine Macrophage ◽  
Concentration Dependent Manner

Glucocorticoid (GC) effectively suppresses immune and inflammatory responses and inhibits the growth of several types of cells, but the role of GC and its receptor on macrophage proliferation is unclear. In our previous work, we found RAW-GR(−) cells (murine macrophage RAW264.7 cells stably transfected with GR-siRNA expression vector by RNA interference) grew faster by about twofold. In this study, we further explored the role and mechanisms of GC/GR on the proliferation of macrophage. We found that the growth of RAW264.7 cells was inhibited by dexamethasone (Dex) in a concentration-dependent manner. The mRNA and protein levels of signal regulatory protein α1 (SIRPA) were induced by GC/GR in RAW264.7 cells and SIRPA expression was decreased remarkably in RAW-GR(−) cells. Overexpression of SIRPA negatively regulated the proliferation of RAW-GR(−) cells, and inhibition of SIRPA expression by a small from RNA interference attenuated Dex-induced proliferation inhibition in RAW264.7 cells. The proliferation inhibition of GC/GR was also found in mouse peritoneal macrophage, which was associated with the increase in SIRPA induced by GC/GR as well. In addition, elevation of the expression of CDK2, cyclinD1, and cyclinB1, but not phosphorylated ERK1/2 and p38, was found in RAW-GR(−) cells. In conclusion, we provided the novel evidences that GC/GR inhibited the growth of RAW264.7 cells and mouse peritoneal macrophage, and the antiproliferative effect of GC/GR on these cells was at least in part a result from GC/GR-induced SIRPA expression. Up-regulation of CDK2, cyclinD1, and cyclinB1 was also related to the increased proliferation of RAW-GR(−) cells.

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E2 in Rat Monocytes Stimulated with Lipopolysaccharide

2003 ◽  
Vol 228 (7) ◽  
pp. 786-794 ◽  
Author(s):  
Wieslaw Kozak ◽  
David M. Aronoff ◽  
Olivier Boutaud ◽  
Anna Kozak
Keyword(s):  
Cell Culture ◽  
Arachidonic Acid ◽  
Negative Feedback ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Concentration Dependent Manner ◽  
Cox 2 ◽  
Cytochrome P 450

Cytochrome P-450 monooxygenase (epoxygenase)-derived arachidonic acid (AA) metabolites, including 11,12-epoxyeicosatrienoic acid (11,12-EET), possess anti-inflammatory and antipyretic properties. Prostaglandin E2 (PGE2), a cyclooxygenase (COX)-derived metabolite of AA, is a well-defined mediator of fever and inflammation. We have tested the hypothesis that 11,12-EET attenuates synthesis of PGE2 in monocytes, which are the cells that are indispensable for induction of fever and initiation of inflammation. Monocytes isolated from freshly collected rat blood were stimulated with lipopolysaccharide (LPS; 100 ng/2 × 105 cells) to induce COX-2 and stimulate generation of PGE2. SKF-525A, an inhibitor of epoxygenases, significantly augmented the lipopolysaccharide-provoked synthesis of PGE2 in cell culture in a concentration-dependent manner. It did not affect, however, elevation of the expression of COX-2 protein in monocytes stimulated with LPS. 11,12-EET also did not affect the induction of COX-2 in monocytes incubated with lipopolysaccharide. However, 11,12-EET suppressed, in a concentration-dependent fashion, the generation of PGE2 in incubates. Preincubation of a murine COX-2 preparation for 0–5 min with three concentrations of 11,12-EET (1, 5, and 10 μM) inhibited the oxygenation of [14C]-labeled AA by the enzyme. The inhibitory effect of 11,12-EET on COX-2 was time-and-concentration-dependent, suggesting a mechanism-based inhibition. Based on these data, we conclude that 11,12-EET suppresses generation of PGE2 in monocytes via modulating the activity of COX-2. These data support the hypothesis that epoxygenasederived AA metabolites constitute a negative feedback on the enhanced synthesis of prostaglandins upon inflammation.

Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1911-1917 ◽  
Author(s):  
Gita T. Kampen ◽  
Susan Stafford ◽  
Tetsuya Adachi ◽  
Tan Jinquan ◽  
Sha Quan ◽  
...  
Keyword(s):  
Map Kinases ◽  
Inflammatory Diseases ◽  
Eosinophil Cationic Protein ◽  
Dependent Manner ◽  
Cationic Protein ◽  
Concentration Dependent Manner ◽  
P38 Inhibitor ◽  
Mitogen Activated Protein ◽  
Integral Role ◽  
Functional Relevance

Abstract Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3 and the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to assess the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay. Chemotaxis was assessed using Boyden microchambers. Eotaxin (10−11 to 10−7 mol/L) induced concentration-dependent phosphorylation of ERK2 and p38. Phosphorylation was detectable after 30 seconds, peaked at about 1 minute, and returned to baseline after 2 to 5 minutes. Phosphorylation of JNK above baseline could not be detected. The kinase activity of ERK2 and p38 paralleled phosphorylation. PD980 59, an inhibitor of the ERK2-activating enzyme MEK (MAP ERK kinase), blocked phosphorylation of ERK2 in a concentration-dependent manner. The functional relevance of ERK2 and p38 was studied using PD98 059 and the p38 inhibitor SB202 190. PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis. We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion.

Stimulation Of Prostacyclin Production In Aortic Endothelial Cells By A Non-Dialysable Serum Factor

1981 ◽  
Author(s):  
E R Hall ◽  
M Rafelson ◽  
K Wu
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Calf Serum ◽  
Dependent Manner ◽  
Freezing And Thawing ◽  
Concentration Dependent Manner ◽  
Aortic Endothelial Cells ◽  
Prostacyclin Production ◽  
Aortic Endothelial

The production of prostacyclin (PGI2) by vascular endothelial cells is thought to be of primary importance in maintaining normal hemostasis. We have investigated the production of prostacyclin in bovine arterial endothelial cells maintained in Dulbecco’s modified Eagle’s medium (DMEM) containing 30% fetal calf serum. Intact, confluent monolayers of endothelial cells (3x106 cells) in passages 2 through 6 were used. The growth medium was removed and the cells were washed in DMEM that did not contain serum. 3 mls of medium alone or containing normal plasma or serum was then added and incubated at 37°C for 15 min. Then, 1 mg of arachidonic acid was added and the cells incubated for an additional hour. The test medium was removed, centrifuged to remove any loose cells and stored at -70°C. To determine the production of PGI2 by the endothelial cells, the medium was assayed for 6-keto-PGF1α, the stable metabolite of PGI2, by radioimmunoassay. The synthesis of prostacyclin by bovine aortic endothelial cells was significantly increased in a concentration dependent manner by both normal platelet poor plasma and normal serum. This increase in prostacyclin production was inhibited by both aspirin and indomethacin, indicating an increase in synthesis rather than the release of PGI2. Furthermore, this increase could be demonstrated in the presence or absence of added arachidonic acid. The active component in plasma and serum was non-dialysable, eliminating the possibility of a small compound such as bradykinin or angiotensin II. This active factor was present after freezing and thawing the plasma and serum and was heat stable (60°C, 5 min). The presence of an endogenous prostacyclin stimulating factor may be significant in the in vivo regulation of prostacyclin production.

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