Oleoylethanolamide induces eosinophilic airway inflammation in bronchial asthma

Kwon Eun-Kyung,최영우,Yoon Il-Hee,Won Ha-Kyeong,심소윤,Lee Hee-Ra,Kim Hyoung Su,예영민,신유섭,박해심,Ban Ga-Young 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils.

A genome-wide by PM₁₀ interaction study identifies novel loci for lung function near <i>BICD1</i> and <i>IL1RN-IL1F10</i> genes in Korean adults

Kim, Hyun-Jin,Seo, Yong-Seok,Sung, Joohon,Chae, Jeesoo,Yun, Jae Moon,Kwon, Hyuktae,Cho, Belong,Kim, Jong-Il,Park, Jin-Ho Elsevier 2020 CHEMOSPHERE - Vol.245 No.-

<P><B>Abstract</B></P> <P>Although several genome-wide interaction studies (GWIS) have been performed in specific European populations to understand the missing link between genetic and environmental factors for lung function, GWIS of Asian samples remain rare. Therefore, we performed a GWIS of exposure to air pollution to identify loci for lung function in Korean adult men. A total of 1826 adult men recruited from two health check-up centers were included in the analysis and the annual mean concentrations of ambient particulate matter with an aerodynamic diameter ≤10 μm (PM<SUB>10</SUB>) were used. In case of forced vital capacity (FVC), one SNP (rs12312730) that passed our genome-wide threshold of <I>p</I>int < 1 × 10–5 was detected in the intronic region of the <I>BICD1</I> gene on chromosome 12. In addition, we found two variants (rs6743376 and rs17042888) located near the <I>IL1RN-IL1F10</I> gene that were involved in the inflammatory response and associated with decreased FVC via interaction with PM<SUB>10</SUB> exposure. A stratified association analysis according to these SNP genotypes showed that PM<SUB>10</SUB> concentrations in subjects with one or two of the risk alleles, compared with those with the non-risk allele, were significantly correlated with a reduction in FVC. This pattern was replicated in another 892 Korean adult samples. The current study reports the first GWIS discovery in an Asian population: the <I>BICD1</I> and <I>IL1RN-IL1F10</I> genes may contribute to the decrease in FVC levels by interacting with PM<SUB>10</SUB> exposure.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Significant interactions between <I>BICD1 or IL1RN-IL1F10</I> and PM<SUB>10</SUB> for FVC were found. </LI> <LI> The several SNPs in these genes were more susceptible to FVC decline by PM<SUB>10</SUB>. </LI> <LI> For FVC, these interaction effects were reproducible in another sample. </LI> </UL> </P>

Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23

Jo, Sungsin,Koo, Bon San,Lee, Bitnara,Kwon, Eunji,Lee, Young Lim,Chung, Heekyoung,Sung, Il-Hoon,Park, Ye-Soo,Kim, Tae-Hwan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bones and its-derived cells from patients with AS showed an increase in ER stress. </LI> <LI> IL-23 cytokine was significantly higher in AS patients than in healthy controls. </LI> <LI> Inducing ER stress in AS exhibited an increase of bone-related genes. </LI> <LI> Inducing ER stress in AS was accompanied with augmentation of IL-23 cytokine. </LI> <LI> ER stress-induced RUNX2 is involved in IL-23 secretion and bone-related genes. </LI> </UL> </P>

일부 한약재의 동종항원에 대한 세포증식 및 살세포반응 억제효과

정영란(Young-Ran Jeong),하미혜(Mee-Hye Ha),김성호(Sung-Ho Kim),조성기(Sung-Kee Jo),변명우(Myung-Woo Byun),조현욱(Hyun-Wook Cho),서권일(Kwon-Il Seo),이성태(Sung-Tae Yee) 한국식품영양과학회 2000 한국식품영양과학회지 Vol.29 No.6

본 실험에서는 동양에서 예로부터 민간요법이나 한방에서 주로 많이 쓰여지고 있는 8가지 종류의 한약재에 대해서 면역억제제로써 사용 가능성을 실험하였다. 그 결과 당귀, 산사, 어성초, 오가피, 황기의 추출물은 동종항원에 반응하는 순수분리 T세포의 증식을 농도 의존적으로 억제시켰다. 또한 이들 T세포의 증식에 있어서 필수적인 IL-2를 포함한 cytokine 즉, IL-2, IL-4, IL-10, IFN-γ의 생산량은 대조군에 비해 실험군에서 유의한 차이가 없었고 특히 T세포 증식에 필수적인 IL-2의 생산량의 변화가 거의 없었다. 이는 한약재에 의한 T세포의 증식억제 효과가 T세포증식에 필수적인 IL-2의 생산량을 억제하기 때문에 일어나는 결과가 아님을 알 수 있었다. 그리고 T세포의 살세포작용 억제를 직접적으로 측정하기 위하여 세포내 LDH의 양을 조사한 결과 모든 대조군에서 50%이상의 살세포작용 억제가 일어났고, 그중 특히 오가피와 황기에서는 100% 살세포작용 억제가 일어났다. 따라서 본 실험에 사용된 당귀, 산사, 어성초, 오가피, 황기 등의 5가지 약재가 부작용 없는 면역억제로써 사용 가능성이 높은 것으로 생각된다. In this experiment, we showed the immunosuppressive effects of herbal plant extracts on the alloantigen reactive proliferation and cytotoxicity. The extracts of Angelica gigas, Crataegus pinnatifida, Houttuynia cordata, Acanthopanax sessiliflorum and Astragalus membranaceus markedly suppressed on the pro- liferation of primary T cells stimulated with allogeneic spleen cells in a dose-dependent manner. The production of IL-2, IFN-γ, IL-4 and IL-10 in the alloreactive primary T cells showed no significant difference in the presence or absence of herbal plants extracts. Also the result of mixed lymphocyte reaction (MLR)-induced cytotoxic T lymphocyte (CTL) showed what is above a certain point 50% inhibition. Specially, the extracts of Acanthopanax sessiliflorum and Astragalus membranaceus com- pletely suppressed the killing activity of CTL. Theses results suggest that the extracts of 5 herbal plants can be used as immunosuppressive agents.

Thymol attenuates the worsening of atopic dermatitis induced by <i>Staphylococcus aureus</i> membrane vesicles

Kwon, Hyo Il,Jeong, Na Hee,Jun, So Hyun,Son, Joo Hee,Kim, Shukho,Jeon, Hyejin,Kang, Sun Chul,Kim, Sang Hyun,Lee, Je Chul Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.59 No.-

<P><B>Abstract</B></P> <P> <I>Staphylococcus aureus</I> membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by <I>S. aureus</I> MVs both <I>in vitro</I> and <I>in vivo</I>. The sub-minimal inhibitory concentrations of thymol disrupted <I>S. aureus</I> MVs. Intact <I>S. aureus</I> MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated <I>S. aureus</I> MVs did not stimulate the expression of these genes. Topical application of thymol-treated <I>S. aureus</I> MVs or treatment with thymol after intact <I>S. aureus</I> MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by <I>S. aureus</I> MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts <I>S. aureus</I> MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by <I>S. aureus</I> MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by <I>S. aureus</I> colonization or infection in the lesions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The subMICs of thymol disrupt <I>S. aureus</I> membrane vesicles (MVs). </LI> <LI> Thymol-treated <I>S. aureus</I> MVs do not induce inflammatory responses in keratinocytes. </LI> <LI> Thymol inhibits worsening of AD-like lesions induced by <I>S. aureus</I> MVs. </LI> </UL> </P>

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

간세포암환자에서 간동맥 화학 색전술 후 발생한 리피오돌에 의한 폐렴 1예

김소이,김유리,허현미,배서은,이명원,최윤정,김고흔,김태헌,유 권,문일환 이화여자대학교 의과대학 2009 EMJ (Ewha medical journal) Vol.32 No.2

Hepatocellular carcinoma(HCC)is one of common causes of cancer-related death in Korea where the majority of HCC patients were Hepaitc B virus(HBV)carriers and have cirrhosis. Transarterial chemoembolization(TACE)is commonly applied to the treatment of multinodular HCC in Korea and careful selection of candidate is important for the risk of various side effects. Besides common side effects as fever, nausea, abdominal pain and elevation of liver enzyme, TACE may predispose to hepatic failure, ischemic cholecystitis, pulmonary embolism, cerebral embolism and pneumonitis. In previous studies, some cases of pulmonary and cerebral embolism cases were reported but lipiodol pneumonitis after TACE was rarely reported. A 65-year-old woman with a multinodular HCC associated with HBV infection, was treated with TACE. Seven days after the procedure, nonspecific respiratory symptoms such as dyspnea and dry cough developed. Chest X-ray and chest computed tomography showed diffuse ground glass opacities in whole lung fields, suggestive of lipiodol pneumonitis. After several days of supportive care with steroid administration, radiologic abnormalities and subjective symptoms were much improved, considered that the disease was compatible with lipiodol pneumonitis.

부산의 한 대학병원에서 분리된 Acinetobacter baumannii의 PER-1 Extended-Spectrum β-Lactamase 생성 현황

김정만,강현경,정석훈,배일권,권수봉,조병규,김둘만,김현주,김아성 대한임상미샐물학회 2004 Annals of clinical microbiology Vol.7 No.1

Corrosion and Oxidation Resistance Behaviors of Ta-Containing Low Alloying Zirconium

Il‑Hyun Kim,Yang‑Il Jung,Byoung‑Kwon Choi,Hyun‑Gil Kim,Jae‑Il Jang 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.8

Zirconium alloys are widely used to fabricate nuclear fuel claddings, and thus is desirable to improve the resistance of suchalloys to corrosion and structural instability. In this study, Ta was used as an alloying element to improve the corrosion andoxidation resistance of zirconium alloys. The model alloy (TaZL) contained 0.03 wt% Ta and other elements with a proportionof less than 1 wt% in total (0.1 wt% Nb, 0.4 wt% Fe, 0.2 wt% Cr) in a zirconium base. The corrosion test involving pressurizedwater at 360 °C and oxidation test involving steam at 1200 °C indicated that TaZL exhibited the lowest weight gains amongthose of compared conventional and advanced Zr alloys. The corrosion and oxidation resistances of TaZL were respectivelyimproved by 4 and 1.5 times compared to the corresponding values of Zircaloy-4. The microstructures of the oxide formedon TaZL were columnar along the oxide growth direction and did not change from columnar to equiaxed, which resulted inthe high resistance of the alloy to corrosion and oxidation.