• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.306-311
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• 2023

The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

• BMB Reports
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• v.28 no.6
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• pp.527-532
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• 1995

Human taurine transporter has 12 transmembrane domains and its molecular weight is 69.6 kDa. The long cytoplasmic carboxy and amino termini might function as regulatory attachment sites for other proteins. Six potential protein kinase C phosphorylation sites have been reported in human taurine transporter. In this report, we studied the effects of phorbol 12-myristate 13-acetate (PMA) and glucocorticoid hormone on taurine transportation in the RAW 264.7, mouse macrophage cell line. When the cells were incubated with $[^{3}H]taurine$ in the presence or absence of $Na^+$ ion for 40 min at $37^{\circ}C$, the [$[^{3}H]taurine$ uptake rate was 780-times higher in the $Na^{+}-containing$ buffer than in the $Na^{+}-deficient$ buffer, indicating that this cell line expresses taurine transporter protein on the cell surface. THP1, a human promonocyte cell line, also showed a similar property. The $[^{3}H]taurine$ uptake rate was not influenced by the inflammatory inducing cytokines such as interleukin-1, gamma-interferon or interleukin-1+gamma-interferon, but was decreased by the PMA in the RAW 264.7 cell line. This suggests that activation of protein kinase C inhibits taurine transporter activity directly or indirectly. The inhibition of $[^{3}H]taurine$ uptake by PMA was time-dependent. Maximal inhibition occurred in one hr stimulation with PMA Increasing the treatment time beyond one h reduced the $[^{3}H]taurine$ uptake inhibition due to the depletion or inactivation of protein kinase C. The cell line also showed concentration-dependent $[^{3}H]taurine$ uptake under PMA stimulation. The phorbol-ester caused 23% inhibition at the concentration of 1 ${\mu}m$ PMA. The inhibition was significant even at a concentration as low as 10 nM PMA The reduced $[^{3}H]taurine$ uptake could be recovered by treatment with glucocorticosteroid hormone. Dexamethasone led to recover of the reduced taurine uptake induced by phorbol-ester, recovering maximally after one hr. This may suggest that macrophage cells require higher taurine concentration in a stressed state, for the secretion of glucocorticoid hormone is increased by hypothalamo-pituitary-adrenocortical (HPA) axis activation in the blood stream.

• The Journal of the Korea Contents Association
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• v.20 no.6
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• pp.124-130
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• 2020

The present study investigated the anti-proliferate and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities of combined treatment with cisplatin and ethyl acetate fractions of Paeonia japonica. Cell Proliferation was detected by the MTS assay and the activity and mRNA expression of MMP-2/-9 were examined by zymography and RT-PCR. As results, cisplatin or p. japonica treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth. Also, the viability of YD-10B cells treated with combination of 200 μM cisplatin and 50 ㎍/ml p. japonica was inhibited to 50% in compared with the cisplatin alone. In PMA-treated YD-10B cells, co-treatment of 200 μM cisplatin with 50 ㎍/ml p. japonica significantly inhibited mRNA expression and protein activation of MMP-2/-9. Therefore, This study suggest that the combination treatment of cisplatin and p. japonica potentiates a promising anti-invasive agent and has more potential anti-cancer drug for oral cancer therapy than cisplatin alone.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.249-255
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• 2007

While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [18F]FDG uptake of stimulated neutrophils. Human neutrophils were stimulated by 100 ng/mL phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [18F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 g/mL) and/or the PI3K inhibitor wortmannin (200 nM). PMA induced a 71.70.9 fold increase in neutrophil oxygen intermediate generation. [18F]FDG uptake was increased to $194.6{\pm} 3.7%$ and hexokinase activity to $145.0{\pm}2.0%$ of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to $35.6{\pm}0.2%$ (p<0.005), but did not inhibit stimulated [18F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA stimulated [18F]FDG uptake to $66.9{\pm}1.6%$ and hexokinase activity to $81.0{\pm}4.2%$ (both P<0.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [18F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. Neutrophil [18F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

• Natural Product Sciences
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• v.23 no.3
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• pp.201-207
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• 2017

Angelica decursiva has been utilised as remedy for controlling the airway inflammatory diseases in folk medicine. We investigated whether nodakenin, columbianadin, and umbelliferone isolated from the roots of Angelica decursiva inhibit the gene expression and production of MUC5AC mucin from human airway epithelial cells. Confluent NCI-H292 cells were pretreated with nodakenin, columbianadin or umbelliferone for 30 min and then stimulated with epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) for 24 h. The MUC5AC mucin gene expression was measured by reverse transcription - polymerase chain reaction (RT-PCR). Production of MUC5AC mucin protein was measured by enzyme-linked immunosorbent assay (ELISA). The results were as follows: (1) Nodakenin did not affect the expression of MUC5AC mucin gene induced by EGF, PMA or $TNF-{\alpha}$. Columbianadin inhibited the expression of MUC5AC mucin gene induced by EGF or PMA. However, umbelliferone inhibited the expression of MUC5AC mucin gene induced by EGF, PMA or $TNF-{\alpha}$; (2) Nodakenin also did not affect the production of MUC5AC mucin protein induced by EGF, PMA or $TNF-{\alpha}$. Columbianadin inhibited the production of MUC5AC mucin protein induced by PMA. However, umbelliferone inhibited the production of MUC5AC mucin protein induced by EGF, PMA or $TNF-{\alpha}$. These results suggest that, among the three compounds investigated, umbelliferone only inhibits the gene expression and production of MUC5AC mucin stimulated by various inducers, by directly acting on airway epithelial cells, and the results might explain the traditional use of Angelica decursiva as remedy for diverse inflammatory pulmonary diseases.

• Natural Product Sciences
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• v.15 no.3
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• pp.139-143
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• 2009

The anaphylactic allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. In this report, I investigated the effect of ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on the anaphylactic allergic reaction and studied its possible mechanisms of action. RFRC inhibited compound 48/80-induced systemic anaphylactic reaction in mice. RFRC dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. In addition, RFRC decreased the gene expression and production of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated human mast cells. These findings provide evidence that RFRC could be a candidate as an anti-allergic agent.

• Natural Product Sciences
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• v.10 no.1
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• pp.24-28
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• 2004

The effects of aqueous extract of Artemisia iwayomogi (Compositae) (AIAE) on the mast cell-dependent allergic and inflammatory reactions were investigated. AIAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in mice. AIAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. AIAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. Moreover, AIAE inhibited the secretion of interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.235-241
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• 1996

The rhamnan sulfate extracted from green algae seaweed, Monostroma nitidum was characterized as activity in vitro culture assay with macrophages from mice. Rhamnan sulfate indicated that F-4-3 fraction enhanced glucose consumption, as well as the production of nitrogen dioxide and tumor necrosis factor(TNF). F-4-3 fraction was also augmented IL-1 secretion from those macrophages. Effects of the pretreatment of peritoneal macrophages with rhamnan sulfate F-4-3 fraction and several polysaccharides as relative standard on the production of H2O2 induced with unopsonized zymosan A were examined. Pretreatment with polysaccharides inhibited the zymosan A mediated H2O2 production by macrophages. The phorbol myristate acetate (PMA) mediated H2O2 production was not affected by the pretreament. These result suggested that pretreatment of rhamnan sulfate interfered with the interaction of macrophages zymosan A. Rhamnan sulfate inhibited zymosan A mediated production of H**O** by macrophages and F-4-3 Fraction was also activator of macrophages.

• Natural Product Sciences
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• v.17 no.3
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• pp.239-244
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• 2011

Immediate-type hypersensitivity is involved in many allergic diseases such as asthma, allergic rhinitis and anaphylaxis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells releases inflammatory mediators, such as histamine and pro-inflammatory cytokines with immune regulatory properties. We investigated the effect of the aqueous extract of Schizonepeta tenuifolia (AEST) (Labiatae) on the immediate-type allergic reaction. AEST inhibited compound 48/80-induced systemic allergic reaction. AEST attenuated immunoglobulin E (IgE)-mediated skin allergic reaction and histamine release from human mast cell line (HMC-1) cells. In addition, AEST decreased the gene expression and secretion of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated HMC-1 cells. Our results indicate that AEST inhibits the mast cell-derived allergic reactions and involvement of histamine and pro-inflammatory cytokines in these effects.

• The Journal of Korean Medicine
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• v.22 no.3
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• pp.1-10
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• 2001

Objectives : The water extract of Nueihyuljunbang (NHJB) has long been used for treatment of ischemic brain damage in Oriental Medicine. However, little is known about the mechanism by which the water extract of NHJB recovers brain cens from ischemic damage. Methods : To elucidate the protective mechanism on ischemic induced cytotoxicity, we investigated the regulation of lipopolysaccharide (LPS) and phorbol-12-myristate-13-acetate (PMA)-induced inducible nitric oxide synthase (iNOS) expression in C6 glial cells. Results : LPS combined PMA treatment for 72 hours in C6 glial cells markedly induced nitric oxide (NO), but treatment of the cells with the water extract of NHJB decreased dose-dependently nitrite formation. In addition, LPS combined PMA treatment for 72 hours induced severe celt death and lactate dehydrogenase (LDH) release in C6 glial cells. However, treatment of the celts with the water extract of NHJB did not induce significant change compared to control cells. Furthermore, the protective effects of the water extract of NHJB were mimicked by the treatment of NGMMA, a specific inhibitor of NOS. LPS combined PMA induced iNOS activation in C6 glial cells caused chromosomal condensation and fragmentation of the nuclei by caspase activation. The treatment of C6 glial cells with the water extract of NHJB might suppress apoptosis via caspase inhibition by regulation of iNOS expression. Conclusions : From the results, we suggest that the protective effects of the water extract of NHJB against ischemic brain damage may be mediated by regulation of iNOS during ischemic condition.