• Title/Summary/Keyword: Suppression

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Brazilin downregulates CCL20 expression via regulation of STAT3 phosphorylation in TNF-α/IL-17A/IFN-γ-induced HaCaT cells (TNF-α/IL-17A/IFN-γ 유도된 HaCaT 세포에서 브라질린의 STAT3 인산화 억제를 통한 CCL20 저해 효과)

  • Kim, Mi Ran;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.185-192
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    • 2021
  • Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

Anti-inflammatory Effects of Hemistepta lyrata Bunge in LPS-stimulated RAW 264.7 Cells through Regulation of MAPK Signaling Pathway (LPS로 유도된 RAW 264.7 대식세포의 염증반응에서 MAPK 신호경로 조절을 통한 지칭개 에탄올 추출물의 항염증 효과)

  • Kim, Chul Hwan;Lee, Young-Kyung;Jeong, Jin-Woo;Hwang, Buyng Su;Jeong, Yong Tae;Oh, Yong Taek;Cho, Pyo Yun;Kang, Chang-Hee
    • Korean Journal of Plant Resources
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    • v.34 no.1
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    • pp.23-30
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    • 2021
  • Hemistepta lyrata Bunge (HL) has been used as a folk remedy to treat cancer, inflammation, bleeding, hemorrhoids and fever, and leaves and young shoots have been used as famine food. Nevertheless, the biological activities and underlying mechanisms of the anti-inflammatory effects remain unclear. In this study, it was undertaken to explore the functions of the aerial part of HL as a suppressor of inflammation by using RAW 264.7 cells. As immune response parameters, the productions of as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines such tumor necrotic factor (TNF)-α and interleukin (IL)-6 were evaluated. Although the release of TNF-α remained unchanged in HL-treated RAW 264.7 cells, the productions of NO, PGE2 and IL-6 were significantly increased at concentrations with no cytotoxicity. Furthermore, HL significantly attenuated the mitogen-activated protein kinases (MAPK) pathway including decreasing the phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases. Collectively, this study provides evidence that HL inhibits the production of major pro-inflammatory molecules in LPS-stimulated RAW 264.7 cells via suppression of ERK and P38 MAPK signaling pathways. These findings suggest that the beneficial therapeutic effects of HL may be attributed partly to its ability to modulate immune functions in macrophages.

Studies on Biological Activity of Woad Extractives (XV) - Antimicrobial and antioxidative activities of extracts from diverse families - (수목 추출물의 생리활성에 관한 연구(XV) - 과별(科別)에 따른 항균 및 항산화 활성 -)

  • Lee, Sung-Suk;Lee, Hak-Ju;Choi, Don-Ha
    • Journal of the Korean Wood Science and Technology
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    • v.32 no.4
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    • pp.8-17
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    • 2004
  • Antifungal, antibacterial, and antioxidative activities of ethanol extracts from 65 families 263 species were investigated to select tree species for the utilization of natural fungicide or preservative resources. The antifungal activities of extracts from wood, leaf and bark were measured as hyphal growth inhibition rate using four plant pathogenic and five wood rotting fungi. High inhibitory effect on the fungi growth was found in five species of Pinaceae (Pinus koraiensis, P. rigida, P. densiflora, P. banksiana. Cedrus deodara), three species of Cupressaceae (Juniperus rigida, J. chinensis, Chamaecyparis obtusa) and three species of Leguminosae (Albizzia julibrisssin, Sophora japonica, Maackia amurensis), respectively. Antibacterial activities of ethanol extracts were determined by means of disc-agar plate diffusion method using three gram-positive and five gram-negative bacteria. The ethanol extracts, which showed prominent effect on the suppression of bacteria growth, were six species of Betulaceae (Carpinus tschonoskii, C. coreana, C. laxiflora, Alnus hirsuta, A. firma, Betula schmidtii), five species of Fagaceae (Castanopsis cuspidata var. sieboldii, Quercus serrata, Q. mongolica, Q aliena, C crenata), four species of Euphorbiaceae (Aleurites fordii, Sapium sebiferum, S japonicum Mallotus japonicus) and three species of Elaeagnaceae (Elaeagnus umbellata, Elaeagnus glanbra, Elaeagnus macrophylla). According to these results, the extracts from Zelkova serrata, Pinus densiflora, Maackia amurensis, Chamaecyparis obtusa and Juniperus chinensis could be available for natural fungicide or food preservatives, because ethanol extracts from these species indicated excellent antifungal and antibacterial activities. In order to test antioxidative activities of ethanol extracts, free radical scavenging method was adopted with 1,1-diphenyl-2-picrylhydrohydrazyl (DPPH). Free radical scavenging activity was proved very high in the extracts of eight species of Rosaceae (Eriobotrya japonica, Prunus takesimensis, P yedoensis, P padus, P armeniaca var. ansu, Chaenomeles sinensis, Stephanandra incisa, Rosa multiflora) and five species of Ericaceae (Rhododenron mucronulatum, R. scblippenbacbii, R. yedoense var. poukhanense, Vaccinium bracteatum, V oldbami), resvectively. It turned out from this study that only six species among 48 species of Rosaceae showed less than 80% free radical scavenging activity. As a consequences, it could be deduced that the components effective on antioxidative activity commonly exist in Rosaceae plant family.

Lysophosphatidic Acid Stimulates SKOV-3 Cell Migration through the Generation of Reactive Oxygen Species via the mTORC2/Akt1/NOX Signaling Axis (리소포스타티드산은 SKOV-3 난소암세포의 mTORC2/Akt1/NOX 신호전달 기전을 통해 활성산소를 형성하고 이를 통해 세포의 이동을 촉진)

  • Eun Kyoung Kim;Seo Yeon Jin;Jung Min Ha;Sun Sik Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.129-137
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    • 2023
  • Reactive oxygen species (ROS) play an essential role in a variety of cellular physiological phenomena. The present study assessed the signaling axis that mediates the lysophosphatidic acid (LPA)-induced migration of SKOV-3 cells. Insulin-like growth factor-1 (IGF-1) stimulated SKOV-3 cell migration in a time- and dose-dependent manner. Similarly, LPA stimulated SKOV-3 cell migration and the phosphorylation of Akt in a time- and dose-dependent manner. The pharmacological inhibition of LPA receptors (LPA1/LPA3) significantly suppressed LPA-induced SKOV-3 cell migration. However, IGF-1-induced SKOV-3 cell migration was not affected by the inhibition of LPA1 and LPA3. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) or Rho-associated kinase (ROCK) significantly suppressed LPA-induced migration, whereas the inhibition of MAPK kinase (MEK) had no effect. Inhibition of PI3K or ROCK completely suppressed LPA-induced ROS generation, and suppression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) or chelation of ROS by N-acetylcysteine (NAC) blocked LPA-induced SKOV-3 cell migration. LPA-induced ROS generation was suppressed by silencing Rictor or Akt1 but not Raptor or Akt2. Silencing Rictor or Akt1 significantly suppressed LPA-induced SKOV-3 cell migration, whereas silencing Raptor or Akt2 had no effect. Finally, the overexpression of the constitutively active form Akt1 (CA-Akt1) significantly enhanced the LPA-induced migration of SKOV-3 cells. Given these results, we suggest that LPA stimulates SKOV-3 cell migration by ROS generation, which is mediated by the mTORC2/Akt1/NOX signaling axis.

Differential Effects of Transforming Growth Factor-β on NKG2D Ligands Expression and NK Cell-mediated Immune Responses in Primary and Metastatic Colon Cancer (원발성 및 전이성 대장암에서 TGF-beta가 NKG2D 리간드 발현과 NK 세포 매개 면역반응에 미치는 영향)

  • Eun-Jung Yun;Yu-Rim Kim;Seong Jun Park;Sang-Yull Lee;Jaeho Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.149-157
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    • 2023
  • Transforming growth factor-β (TGF-β) is a multifunctional cytokine that affects not only the survival and growth of cancer cells but also the activity of immune cells. Although it has been generally accepted that cancer cell-derived TGF-β could promote the survival and growth of early cancer cells and have immunosuppressive roles, it has been known that TGF-β has differential effects according to the type or stage of cancer cells. Therefore, it is hard to clearly define its role in cancer progression and immune responses. This study investigated the effects of TGF-β signaling on the expression of five NKG2D ligands and the NK cell-mediated anticancer immune response in the primary colon cancer cell line KM12C and its two metastatic cell lines, KM12SM and KM12L4A. At the surface protein level, exogenous TGF-β decreased the expression of MICA, MICB, ULBP1, and ULBP2, and galunisertib increased the expression of MICA, MIAB, ULBP1, ULBP2, and ULBP3 in KM12C. However, KM12SM and KM12L4A showed no significant changes in the expression of NKG2DLs after treatment with TGF-β or galunisertib. TGF-β signaling inhibition via galunisertib improved the NK cell-mediated anticancer immune response against KM12C but did not show a significant response to KM12SM and KM12L4A. Therefore, the suppression of TGF-β signaling could improve the NK cell-mediated anticancer immune response against KM12C. However, an increase in NKG2DLs expression and an enhanced NK cell-mediated cancer immune response is hard to expect due to the alteration of TGF-β signaling in KM12SM and KM12L4A.

Chinese Agrarian Resistance and A New Mediation of State-Society Relationship (중국 농민저항과 국가-사회 관계의 새로운 조정)

  • Lee, Ki-Hyun
    • Journal of International Area Studies (JIAS)
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    • v.15 no.1
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    • pp.61-82
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    • 2011
  • Public resistance is an essential factor of the democratization process. Due to this, public resistance has been recognized as an important element in discussing the democratization of China. Recently in China, and a new era of resistance especially the agrarian resistance has been being expanded. This paper identifies trends and characteristics of that. With searching changes in the relationship between the nation and the societies in China, we will check whether democratization can be built from the whole bottom of the nation's ideology or not. It is a paradox of china's economic growth that the peasant uprising increased is a factor to the growth. The farmers' smoldering discontent exploded with rage because rural communities have been forced to sacrifice during the growth. The authoritarian party-state system in China has been faced with the limits in calming the peasant revolt down with the traditional suppression and restriction. Even though the party-state system in China has accepted farmers' dissatisfaction somewhat, and it has tried to improve its image of a benevolent government and pursued buying stability strategy, the gap between urban and rural areas has been expanded in the sustainable economic development and modernization process, therefore the authorities could not soothe the farmers' sense of alienation. Accordingly, the peasant revolt has not flickered out easily, and has been getting uncontrolled across China. Resistance characteristics of Chinese farmers have also changed. In the past, they had been sporadic and indirect ways, whereas in recent years, they have changed into organized and active ways. Of course, it is generally evaluated that the party-state system has sustained a strong social control so far. Buying stability strategy has prevented farmers' complaints from spreading to a threat to its regime, because civil societies in rural areas have still weak foundations from being formed. The party-state system, because of tensions and conflicts, will control the growing powers of civil societies in rural areas with institutionalization of interaction between the nation and the societies, and they will induce street protests to legalized struggle for a while. However, the relationship between the state and the societies has already started new rearrangement, in terms of that the conflicts between the state and rural communities have continued, and the changes of resistance ways.

Synthesis of Uniform Silica Nanoparticles using Tap, Industrial, and Stream water and Their Application to Electro-responsive Smart Fluid System (상수, 공업용수, 및 하천수를 활용한 균일한 실리카 나노입자 합성 및 전기감응형 스마트유체로의 응용)

  • Ha-Yeong Kim;Suk Jekal;Neunghi Lee;Minki Sa;Dong Hyun Kim;Min Sang Kim;Jiwon Kim;Chang-Min Yoon
    • Journal of the Korea Organic Resources Recycling Association
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    • v.31 no.1
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    • pp.47-56
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    • 2023
  • This study describes the successful synthesize strategy for the silica nanoparticles utilizing various water sources, including tap, industrial, and stream waters without using deionized water. Also, as-synthesized silica nanoparticles are employed as dispersive materials for the electro-responsive smart fluid application. Specifically, homogeneous silica nanoparticles with sizes of 500-700nm are successfully prepared in large scale at once (ca. 12.0 g) with the described experimental method and showing similar structural and chemical characteristics with silica nanoparticles synthesized using the deionized water. The size of silica nanoparticles are varied according to the ion conductivity differences of tap, industrial, stream water, and deionized water. The size of silica nanoparticles decresed with the increased ion conductivity, indicating the ion suppression of growth of silica nanoparticles. Moreover, as-synthesized silica nanoparticles from various water sources of electro-responsive characteristic are investigated by the smart fluid application. The smart fluids containing silica nanoparticles synthesized by tap, industrial, and stream water exhibited higher shear stress compared to the deionized water, owing to the more rigid fibril-like structures formed by the smaller silica nanoparticles. Conclusively, uniform silica nanoparticles from various water sources without any purification are able to successfully prepared without usage of deionized water and resulting silica nanoparticles manifested higher electro-responsive performance.

[ $^1H$ ] MR Spectroscopy of the Normal Human Brains: Comparison between Signa and Echospeed 1.5 T System (정상 뇌의 수소 자기공명분광 소견: 1.5 T Signa와 Echospeed 자기공명영상기기에서의 비교)

  • Kang Young Hye;Lee Yoon Mi;Park Sun Won;Suh Chang Hae;Lim Myung Kwan
    • Investigative Magnetic Resonance Imaging
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    • v.8 no.2
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    • pp.79-85
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    • 2004
  • Purpose : To evaluate the usefulness and reproducibility of $^1H$ MRS in different 1.5 T MR machines with different coils to compare the SNR, scan time and the spectral patterns in different brain regions in normal volunteers. Materials and Methods : Localized $^1H$ MR spectroscopy ($^1H$ MRS) was performed in a total of 10 normal volunteers (age; 20-45 years) with spectral parameters adjusted by the autoprescan routine (PROBE package). In all volunteers, MRS was performed in a three times using conventional MRS (Signa Horizon) with 1 channel coil and upgraded MRS (Echospeed plus with EXCITE) with both 1 channel and 8 channel coil. Using these three different machines and coils, SNRs of the spectra in both phantom and volunteers and (pre)scan time of MRS were compared. Two regions of the human brain (basal ganglia and deep white matter) were examined and relative metabolite ratios (NAA/Cr, Cho/Cr, and mI/Cr ratios) were measured in all volunteers. For all spectra, a STEAM localization sequence with three-pulse CHESS $H_2O$ suppression was used, with the following acquisition parameters: TR=3.0/2.0 sec, TE=30 msec, TM=13.7 msec, SW=2500 Hz, SI=2048 pts, AVG : 64/128, and NEX=2/8 (Signa/Echospeed). Results : The SNR was about over $30\%$ higher in Echospeed machine and time for prescan and scan was almost same in different machines and coils. Reliable spectra were obtained on both MRS systems and there were no significant differences in spectral patterns and relative metabolite ratios in two brain regions (p>0.05). Conclusion : Both conventional and new MRI systems are highly reliable and reproducible for $^1H$ MR spectroscopic examinations in human brains and there are no significant differences in applications for $^1H$ MRS between two different MRI systems.

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The Effects of Isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl]acetate (YH439) on Potentiated Carbon Tetrachloride Hepatotoxicity (상승적 화학적 간독성에 미치는 YH439의 영향)

  • Kim, Sang-Geon;Cho, Joo-Youn
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.407-416
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    • 1996
  • The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

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Fly Ash Application Effects on CH4 and CO2 Emission in an Incubation Experiment with a Paddy Soil (항온 배양 논토양 조건에서 비산재 처리에 따른 CH4와 CO2 방출 특성)

  • Lim, Sang-Sun;Choi, Woo-Jung;Kim, Han-Yong;Jung, Jae-Woon;Yoon, Kwang-Sik
    • Korean Journal of Soil Science and Fertilizer
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    • v.45 no.5
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    • pp.853-860
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    • 2012
  • To estimate potential use of fly ash in reducing $CH_4$ and $CO_2$ emission from soil, $CH_4$ and $CO_2$ fluxes from a paddy soil mixed with fly ash at different rate (w/w; 0, 5, and 10%) in the presence and absence of fertilizer N ($(NH_4)_2SO_4$) addition were investigated in a laboratory incubation for 60 days under changing water regime from wetting to drying via transition. The mean $CH_4$ flux during the entire incubation period ranged from 0.59 to $1.68mg\;CH_4\;m^{-2}day^{-1}$ with a lower rate in the soil treated with N fertilizer due to suppression of $CH_4$ production by $SO_4^{2-}$ that acts as an electron acceptor, leading to decreases in electron availability for methanogen. Fly ash application reduced $CH_4$ flux by 37.5 and 33.0% in soils without and with N addition, respectively, probably due to retardation of $CH_4$ diffusion through soil pores by addition of fine-textured fly ash. In addition, as fly ash has a potential for $CO_2$ removal via carbonation (formation of carbonate precipitates) that decreases $CO_2$ availability that is a substrate for $CO_2$ reduction reaction (one of $CH_4$ generation pathways) is likely to be another mechanisms of $CH_4$ flux reduction by fly ash. Meanwhile, the mean $CO_2$ flux during the entire incubation period was between 0.64 and $0.90g\;CO_2\;m^{-2}day^{-1}$, and that of N treated soil was lower than that without N addition. Because N addition is likely to increase soil respiration, it is not straightforward to explain the results. However, it may be possible that our experiment did not account for the substantial amount of $CO_2$ produced by heterotrophs that were activated by N addition in earlier period than the measurement was initiated. Fly ash application also lowered $CO_2$ flux by up to 20% in the soil mixed with fly ash at 10% through $CO_2$ removal by the carbonation. At the whole picture, fly ash application at 10% decreased global warming potential of emitted $CH_4$ and $CO_2$ by about 20%. Therefore, our results suggest that fly ash application can be a soil management practice to reduce green house gas emission from paddy soils. Further studies under field conditions with rice cultivation are necessary to verify our findings.