• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.79-86
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• 2001

Recent clinical studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (ATRA). However, most patients who receive continuous treatment with ATRA relapse and develop ATRA-resistant leukemia. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we investigated the strategies to overcome ATRA resistance of APL cells by inducing the differentiation of DCs from human leukemic cell lines for the developtment of adoptive immunotherapy. CD83 was used as a mature DC marker in this study and the expression of CD83 mRNA was determined by RT-PCR method. The promyelocytic leukemic cell line HL-60, B lymphoblast cell lines RPMI 7666 and NC-37 could be induced to dendritic cells in vitro. Treatment of HL-60 with phorbol 12-myristate 13-acetate (PMA) resulted in the expression of myeloid-related DC phenotypes, while treatment of RPMI 7666 with fms-like tyrosine kinase 3 ligand (Flt3-ligand, FL) and treatment of NC-37 with PMA and FL led to the expression of lymphoid-related DC phenotypes. In conclusion, myeloid-related DC phenotypes and lymphoid-related DC phenotypes could be generated from HL-60, NC-37 and RPMI 7666 cell lines, respectively. These DC phenotypes can potentially be used to generate antileukemic T cells in vitro for adoptive immunotherapy.

• Biomolecules & Therapeutics
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• 제13권4호
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• pp.251-255
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• 2005

In the present study, we tried to investigate whether protein kinase C (PKC) activator, phorbol 12-Myristate 13-Acetate (PMA), and PKC inhibitors, $G\"{o}-6976$, Ro-31-8220 and rottlerin significantly affect basal mucin relesed from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3H$-glucosamine for 24 hr and chased for 30 min in the presence of each agent to assess the effects on $^3H$-mucin release. The results were as follows: (1) PMA increased mucin release from cultured HTSE cells, during 30 min of treatment period; (2) However, $G\"{o}-6976$, Ro-31-8220 and rottlerin did not significantly affect mucin release, during 30 min of treatment period. This finding suggests, at least in part, that PKC might playa minor role in the signaling pathways involved in basal - physiological or constitutive - mucin release from airway goblet cells, although further studies are needed.

• Journal of Evidence-Based Herbal Medicine
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• 제1권1호
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• pp.13-18
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• 2008

Polygoni cuspidati Rhizoma (PCRH) has been used in treatment of menoxenia, skin burn, gallstone, hepatitis, hyperlipidaemia, favus athlete's foot, supperative dermatitis and inflammation. However, its effect in experimental models remains unknown. In this present study, the effect of PCRH for stability on mast cell was analyzed. Two g/kg PCRH inhibited the compound 48/80-induced anaphylaxis by 75%. In addition, PCRH inhibited the tumor necrosis factor-$\alpha$ and interleukin-8 secretion as compared with the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 stimulated human mast cell line, HMC-1 cells. These results suggested PCRH may inhibit mast cell-mediated anaphylactic reaction.

• 대한한방소아과학회지
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• 제26권2호
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• pp.13-24
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• 2012

Objectives NJ is being used to treat inflammatory diseases in Korea. In this study, we attempted to evaluate the effects of NJ on atopic dermatitis (AD)-like lesions and mast cell-mediated allergy inflammation in vivo and in vitro. Methods and Results We investigated to ascertain the pharmacological effects of NJ on 2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo conditions. Additionally, to find possible explanations for the anti-inflammatory mechanisms of NJ, we evaluated the regulatory effects of NJ on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). Conclusions NJ inhibited the production of the inflammatory cytokines (IgE, IL-6, IL-8 and TNF-${\alpha}$) significantly in vivo and in vitro.

• Environmental Analysis Health and Toxicology
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• 제15권3호
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• pp.69-80
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• 2000

ADP-rubosylation may be involved in the process of macrophage activation. Nitric oxide (NO) has emerged as an important intracellular and interacellular regulatory molecule with function as diverse as vasodilation, neural communication or host defense. NO is derived from the oxidation of the terminal guanidino nitrogen atom of L-arginine by the NADPH -dependent enzyme, nitric oxide synthase (NOS) which is one of the three different isomers in mammalian tissues. Since NO can exert protective or regulatory functions in the cell at a low concentration while toxic effects at higher concentrations, its role may be tightly regulated in the cell. Therefore, this paper was focused on signal transduction pathway of NO synthesis, role of endogenous TGF-$\beta$ in NO production. effect of NO on superoxide formation. Costimulation of murine peritoneal macrophages with interferon-gamma (IFN-γ) and phorbol 12-myristate 13-acetate (PMA) increased both NO secretion and mRNA expression of inducible nitric oxide synthase (iNOS) when PMA abolished costimulation. Pretreatmnet of the cells with PMA abolished costimuation effects due to the depletion of protein kinase C (PKC) activities . The involvement of PKC in NO secretion could be further confirmed by PKC inhibitor, stauroprine, and phorbol ester derivative, phorbol 12,13-didecanoate. Addition of actinomycine D in IFN-γ plus PMA stimulated cells inhibited both NO secretion and mRNA expression of iNOS indication that PMA stabilizes mRNA of iNOS . Exogenous TGF-$\beta$ reduced NO secretion in IFN -γ stimulated murine macrophages. However addition of antisense oligodeoxynucleotide (ODN) to TGF-$\beta$ to this system recovered the ability of NO production and inhibited mRNA expression of TGF-$\beta$. ACAS interactive laser cytometry analysis showed that transportation of FITC -labeled antisense ODN complementary to TGF-$\beta$ mRNA could be observed within 5 min and reached maximal intensity in 30 min in the murine macrophage cells. NO released by activated macrophages inhibits superoxide formation in the same cells . This inhibition nay be related on NO-induced auto -adenosine diphosphate (ADP) -ribosylation . In addition, ADP-ribosylation may be involved in the process of macrophage activation .

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.185-193
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• 1997

The characteristics of $Na^+$-dependent cycloleucine uptake was investigated in OK cells with regard to substrate specificity and regulation by protein kinase C (PKC). Inhibition studies with different synthetic and natural amino acids showed a broad spectrum affinity to neutral amino acids regardless of their different side chains including branched or aromatic, indicating that the $Na^+$-dependent cycloleucine uptake in OK cells is mediated by System $B^o$ or System $B^o$-like transporter rather than the classical System A or ASC. Phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate, but not $4{\alpha}-PMA$ elicited a time-dependent biphasic stimulation of $Na^+$-dependent cycloleucine uptake, which produced early transient peak at 30 min and late sustained peak at 180min. Both the early and late stimulations by PMA were due to an increase in Vmax and not due to a change in Km. PKC inhibitors blocked both the early and late stimulation by PMA, while protein synthesis inhibitors blocked the late stimulation only. These results suggest the existence and regulation by PKC of System $B^o$ or System $B^o$-like broad spectrum transport system for neutral amino acids in OK cells.

• 한국식품과학회지
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• 제48권6호
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• pp.590-596
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• 2016

본 연구에서는 우리나라에서 가장 많이 재배되고 있는 캠벨어얼리 포도 품종에서 포도가지를 대상으로 산화방지, 항염증 및 항가려움증 효과를 검증하고 활성물질을 나타내는 지표물질을 추적 조사하였다. 그 결과 포도가지 추출물의 총 폴리페놀과 총 플라보노이드 함량은 각각 $201.42{\pm}4.16$과 $11.85{\pm}0.44mg\;GAE/g$으로 조사되었다. 또한 캠벨어얼리 포도가지 추출물의 ABTS와 DPPH 라디칼 소거 활성은 각각 $45.60{\pm}0.09$ ($IC_{50}$)과 $299.13{\pm}0.22$ ($IC_{50}$)으로 나타나 산화방지 활성이 우수하였다. 게다가 캠벨어얼리 포도가지 추출물은 지방질다당류로 활성화된 RAW 264.7 세포에서 전염증성 매개물인 산화질소와 프로스타글란딘 $E_2$를 iNOS와 COX-2 분자 발현 억제를 통하여 억제하였고, 전염증성 사이토카인인 인터류킨-1베타와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 더욱이 phorbol 12-myristate 13-acetate (PMA)와 calcium ionophore A23187로 활성화된 인간 유래 비만세포인 HMC-1 세포에서 종양괴사인자-알파와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 마지막으로 Compound 48/80으로 유도되는 마우스 가려움증을 캠벨어얼리 포도가지 추출물은 효과적으로 억제하였다. 이러한 캠벨어얼리 추출물에서 활성을 나타내는 물질을 추적한 결과 레스베라트롤의 함량이 높게 검출되었다. 그러므로 본 연구의 결과를 종합해 볼 때 캠벨어얼리 포도가지 추출물은 아토피 질환에서 나타나는 염증과 가려움증을 효과적으로 제어할 수 있는 효과적인 소재임을 제시하였다.

• Tuberculosis and Respiratory Diseases
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• 제70권3호
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• pp.218-223
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• 2011

Background: We investigated whether curcumin and genistein affect the MUC5AC mucin production from human airway epithelial cells that is induced by phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). Methods: Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or TNF-${\alpha}$ for 24 hours. MUC5AC mucin production was measured by an ELISA. Results: (1) Curcumin dose-dependently inhibited the production of MUC5AC mucin that was induced by PMA or TNF-${\alpha}$; (2) Genistein inhibited PMA-induced MUC5AC mucin production. However, it did not decrease TNF-${\alpha}$-induced MUC5AC mucin production. Conclusion: These results suggest that curcumin and genistein inhibit the production of airway mucin induced by PMA.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.431-436
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• 2020

In this study, diclofenac, a non-steroidal anti-inflammatory drug, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. The human respiratory epithelial NCI-H292 cells were pretreated with diclofenac for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of diclofenac on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Diclofenac suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest diclofenac regulates the gene expression and production of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

• Natural Product Sciences
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• 제25권3호
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• pp.248-254
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• 2019

In the present study, we investigated whether quercitrin, quercetin and afzelin derived from Houttuynia cordata affect the production and gene expression of MUC5AC mucin from airway epithelial cells. Confluent NCI-H292 cells were pretreated with quercitrin, quercetin or afzelin for 30 min and then stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA) for 24 h. The MUC5AC mucin gene expression and production were measured by RT-PCR and ELISA, respectively. The results were as follows: (1) Quercitrin, quercetin and afzelin inhibited EGF- and PMA-induced MUC5AC mucin production from NCI-H292 cells; (2) The three natural products also decreased EGF- and PMA-induced MUC5AC mucin gene expression in NCI-H292 cells. These results suggest that quercitrin, quercetin and afzelin showed the regulatory effect on the steps of gene expression and production of mucin, by directly acting on airway epithelial cells.