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        IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid

        Park, Sun Hong,Baek, Seung-Il,Yun, Jieun,Lee, Seungmin,Yoon, Da Young,Jung, Jae-Kyung,Jung, Sang-Hun,Hwang, Bang Yeon,Hong, Jin Tae,Han, Sang-Bae,Kim, Youngsoo American Association of Immunologists 2015 Journal of Immunology Vol. No.

        <P>Mice lacking the IL-1R-associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus D-galactosamine-induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/D-galactosamine-challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist-, IL-1 alpha-, or high-mobility group box-1-stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-kappa B or AP-1. CGA consequently attenuated protein or mRNA levels of NF-kappa B/AP-1 target genes encoding TNF-alpha, IL-1 alpha, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity-related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses.</P>

      • KCI등재후보

        升麻葛根湯의 항히스타민 효과 및 IL-4와 GM-CSF 발현에 미치는 영향

        김홍배,김원일,이승연,Kim, Hong-Bae,Kim, Own-Il,Lee, Seung-Yeon 대한한방소아과학회 2006 대한한방소아과학회지 Vol.20 No.1

        We investigated the effect of Sungmagalkun-tang (SGT) on the allergy. We conformed compound 48/80-induced active systemic anaphylatic shock, anti-dinitrophenyl IgE-mediated passive cutaneous anaphylaxis and ovalbumin-induced anaphylatic shock. Also observed IL-4 and GM-CSF mRNA expression in ovalbumin-induced allergic lung tissue and RBL-2H3. Histamine release is measured in RBL-2H3. SGT inhibited active systemic anaphylatic shock, passive cutaneous anaphylaxis and ovalbumin-induced anaphylatic shock by oral administration. We observed that SGT was concentration-dependently reduced IL-4 and GM-CSF mRNA expression in ovalbumin-induced allergic lung tissue and RBL-2H3 by SGT. In addition, SGT reduced histamine release in RBL-2H3. These results indicate that SGT has anti-histamic effect and controls IL-4 and GM-CSF mRNA expression on allergy.

      • SCISCIESCOPUS

        A novel, topical, nonsteroidal, TRPV1 antagonist, PAC-14028 cream improves skin barrier function and exerts anti-inflammatory action through modulating epidermal differentiation markers and suppressing Th2 cytokines in atopic dermatitis

        Lee, Ji-Hae,Choi, Chang Soon,Bae, Il-Hong,Choi, Jin Kyu,Park, Young-Ho,Park, Miyoung Elsevier 2018 JOURNAL OF DERMATOLOGICAL SCIENCE Vol.91 No.2

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown.</P> <P><B>Objective</B></P> <P>Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD.</P> <P><B>Methods</B></P> <P>AD-like dermatitis was induced in hairless mice by repeated oxazolone (Ox) challenges to hairless mice. The functional studies concerning skin barrier function, anti-inflammatory action, and molecular mechanism by TRPV1 antagonism were conducted by histopathological assays, ELISA, qPCR, western blotting, and skin blood flow measurement.</P> <P><B>Results</B></P> <P>Topically administered TRPV1 antagonist, PAC-14028 (Asivatrep: C<SUB>21</SUB>H<SUB>22</SUB>F<SUB>5</SUB>N<SUB>3</SUB>O<SUB>3</SUB>S), improved AD-like dermatitis and skin barrier functions, and restored the expression of epidermal differentiation markers. In addition, the PAC-14028 cream significantly inhibited cutaneous inflammation by decreasing the expression of serum IgE, and the epidermal expression of IL-4, and IL-13 in Ox-AD mice. These results may provide a novel insight into the molecular mechanism of PAC-14028 cream involved in anti-inflammatory effects and skin barrier functions by suppressing the multiple signaling pathways including IL-4/-13-mediated activation of JAK/STAT, TRPV1, and neuropeptides.</P> <P><B>Conclusion</B></P> <P>PAC-14028 cream can be a potential therapeutic tool for the treatment of chronic inflammation and disrupted barrier function in patients with AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PAC-14028 1% topical cream is an anti-inflammatory, non-steroidal TRPV1 antagonist. </LI> <LI> PAC-14028 cream treatment reduced AD-like symptoms and improved skin barrier functions in Ox-induced <I>in vivo</I> murine model. </LI> <LI> PAC-14028 suppressed the signaling pathways including IL-4/-13 mediated activation of JAK/STAT, TRPV1, and neuropeptides. </LI> </UL> </P>

      • Ginsenoside Rg1 enhances CD4^(+) T-cell activities and modulates Th1/Th2 differentiation

        Lee, Eui-joon,Ko, Eunjung,Lee, Jinwoo,Rho, Samwoong,Ko, Seonggyu,Shin, Min-Kyu,Min, Byung-il,Hong, Moo-Chang,Kim, Si-young,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

        Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper(Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4 T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4^(+) T cells, but augmented CD4^(-) T-cell proliferation upon activation with anti-CD3/anti-CD28 autibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4^(-) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4^(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4^(+) T cells under Th2 skewed condition, while decreasing IFN-ysecretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naive CD4^(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4^(-) T-cell activity, as well as the correction of Th1-dominant pathological disorders.

      • KCI등재

        UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

        Minjung Chae,Eui-dong Son,Il-Hong Bae,조은경,Hyoung-June KIM,Ji-Yong Jung 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

        Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

      • 디지털 이미지 보호를 위한 효과적인 웨이브릿 변환

        홍성표,박영옥,송기범,배일호,이준 조선대학교 전자정보통신연구소 2002 電子情報通信硏究所論文誌 Vol.5 No.2

        The use of digital imaging technique and digital contents based on internet has grown rapidly for last several years, and the needs of digital image protection become more important. For the purpose of copyright protection on digital image, the verification of authentication techniques like content authentication, ownership authentication, illegal copy and etc are needed. Digital watermarking, the invisible encryption technique to insert digital watermark into image, the sophisticated perceptual information should be used for providing transparency and robustness of images on watermarking process. In this paper, we implement the algorithm for preventing forged attack, ownership protection and authentication by transforming the wavelet algorithms in frequency domain in terms of human visual system.

      • 폐혈관상이 유지된 선천성 낭성 선종양 기형

        배일헌,한기석,차상훈,김성진,박길선,이건국,홍장수 충북대학교 의과대학 충북대학교 의학연구소 2003 忠北醫大學術誌 Vol.13 No.2

        선천성 낭성 선종양 기형은 태생 16주 이후 말단세기관지의 형성이 중단되어 미성숙기관지들과 중배엽성분들이 과도하게 증식하여 발생하는 드문 선천성 폐질환이다. CT소견은 낭종의 크기 숫자, 내용물 등에 따라 다양하나, 병변내에 정상적인 폐혈관이 보인 예는 전세계적으로 보고된 적이 없었다. 저자들은 역동적 흉부 CT상 균일한 저음영의 병변내에 정상 폐혈관상이 유지된 선천성 낭성 선종양 기형 1예를 경험하였기에 보고한다. Congenital cystic adenomatoid malformation(CCAM) is a rare pulmonary disease that is thought to be developed by abnormal proliferation of immature alveoli and other mesenchymal component from the abrupt halting of the terminal alveoli formation after 16 weeks of gestation. On CT scan, there are no consistencies regarding to size, numbers, and its contents but no cases were reported in past showing normal pulmonary vascularities. We reports a case of CCAM that showed normal pulmonary vascularities within the hypodense lesions on a dynamic chest CT

      • KCI등재

        열공형과 비열공형 피질하 혈관성 치매에서 위험인자의 차이에 관한 비교 연구

        배희준,정지향,유경호,나덕렬,김상윤,최경규,양동원,손의주,이상도,김재우,박경원,김응규,이재홍,박미영,한일우,함동석,최문성,하충건,최성혜,이애영,이병철,한설희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.2

        Backgrounds and Objectives: Vascular dementia is a group of dementing disoders arising from various stroke syndrome. Among these. subcortical ischemic vascular dementia (SIVD) is regarded as a relatively distinct clinical entity. However, MRI patterns of SIVD are not homogenous. In some patients, lacunes are dominant, and in others, subcortical white matter changes are. This study was designed to compare risk factor profiles between SIVD with and without multiple lacunes. Methods: We divided 47 subjects (22 males, mean age. 68 years) recruited from VADAPET (Multicenter Trial For Evaluation Of The Changes In the PET Images Of Subcortical Vascular Dementia Patient) study into two groups one with more than 5 lacunes in deep gray matter (lacune group) and the other with 5 or less(non-lacune group) Clinical characteristics and laboratory findings of two groups were compared. Results: Nineteen of 47 patients (40%) belonged to the lacune group. The lacune and non-lacune groups d d not differ in the following variables: age, hypertension, diabetes mellitus, hyperlipidemia heart disease, history of stroke or TIA, history of trauma or major surgery, family history of hypertension stroke, or dementia, age at diagnosis of dementia, body mass index, white blood cell count, ESR, CRP, fibrinogen, hemoglobin A1C, total cholesterol. LDL cholesterol creatinine, proteinuria, glucosuria, and microhematuria. However, male sex, smoking alcohol. hemoglobin, and HDL cholesterol were possibly associated more with lacune group SIVD than with non-lacune group (p<0 1) Multivariate analyses revealed that smoking, hemoglobin, and HDL cholesterol were independent predictors of SIVD with multiple lacunes Conclusion: Our study suggests that SIVD with multiple lacunes may be significantly different in smoking habits hemoglobin, and HDL cholesterol from SIVD without multiple lacunes.

      • 기흉 후 발생한 뇌동맥 공기 색전증 : 1예 보고

        배일헌,한기석,차상훈,김성진,박길선,홍장수 충북대학교 의과대학 충북대학교 의학연구소 2003 忠北醫大學術誌 Vol.13 No.2

        뇌혈관내 공기 색전증은 뇌혈관 조영술, 혈관내 도자술 시행시 발생하여 매우 심각한 합병증을 유발할 수 있다. 그러나 기흉의 합병증으로 발생한 경우는 보고된 적이 없다. 저자들은 기흉에 의하여 발생한 뇌혈관내 공기 색전증 1예를 경험하였기에 보고한다. Cerebral arterial air embolism is a potentially fatal event that may occur during the cerebral angiography and intravascular catheterization. The CT findings of cerebral arterial air embolism following pneumothorax have not been reported. We report a case of cerebral arterial air embolism following pneumothorax, and describe the CT findings.

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