Glyoxal-induced exacerbation of pruritus and dermatitis is associated with <i>staphylococcus aureus</i> colonization in the skin of a rat model of atopic dermatitis

Han, Rafael Taeho,Kim, Hye Young,Ryu, Hyun,Jang, Wooyoung,Cha, Seung Ha,Kim, Hyo Young,Lee, JaeHee,Back, Seung Keun,Kim, Hee Jin,Na, Heung Sik Elsevier 2018 Journal of dermatological science Vol.90 No.3

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induced aggravation of AD have hardly been studied.</P> <P><B>Objective</B></P> <P>To investigate the molecular mechanisms by which glyoxal, a PM-forming organic compound, exacerbates the symptoms of AD induced by neonatal capsaicin treatment.</P> <P><B>Methods</B></P> <P>Naïve and AD rats had been exposed to either fresh air or vaporized glyoxal for 5 weeks (2 h/day and 5 days/week) since one week of age. Pruritus and dermatitis were measured every week. The skin and blood were collected and immunological traits such as Staphylococcus aureus skin colonization, production of antimicrobial peptides and immunoglobulin, and mRNA expression of inflammatory cytokines were analyzed.</P> <P><B>Results</B></P> <P>Exposure to glyoxal aggravated pruritus and dermatitis in AD rats, but did not induce any symptoms in naïve rats. Staphylococcus aureus skin colonization was increased in the skin of both naïve and AD rats. Expression of antimicrobial peptides such as LL-37 and β-defensin-2 was also increased by exposure to glyoxal in the skin of both naïve and AD rats. The mRNA expression of Th1-related cytokines was elevated on exposure to glyoxal. However, serum immunoglobulin production was not significantly changed by exposure to glyoxal.</P> <P><B>Conclusion</B></P> <P>In AD rats, exposure to glyoxal exacerbated pruritus and cutaneous inflammation, which was associated with increased colonization of <I>S. aureus</I> and subsequent immunological alterations in the skin.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Exposure to glyoxal aggravated the symptoms in AD rats, but did not induce AD in naïve rats. </LI> <LI> <I>S. aureus</I> skin colonization and subsequent expression of antimicrobial peptides were increased after exposure to glyoxal. </LI> <LI> Exposure to glyoxal elevated the production of Th1-related cytokines such as TNF-α and IFN-γ in the AD lesional skin. </LI> </UL> </P>

Deficiency of iNOS Does Not Prevent Isoproterenol-induced Cardiac Hypertrophy in Mice

Cha, Hye-Na,Hong, Geu-Ru,Kim, Yong-Woon,Kim, Jong-Yeon,Dan, Jin-Myoung,Park, So-Young The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-${\beta}$ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-${\beta}$ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice

Hye-Na Cha,Jung Hyun Choi,Yong-Woon Kim,Jong-Yeon Kim,Myun-Whan Ahn,So-Young Park 대한생리학회-대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.6

The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-Ղ, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-Ղ, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.

Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice

Cha, Hye-Na,Choi, Jung-Hyun,Kim, Yong-Woon,Kim, Jong-Yeon,Ahn, Myun-Whan,Park, So-Young The Korean Society of Pharmacology 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.6

The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-${\beta}$, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-${\beta}$, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.

Deficiency of iNOS Does Not Prevent Isoproterenol-induced Cardiac Hypertrophy in Mice

Hye-Na Cha,Geu-Ru Hong,Yong-Woon Kim,Jong-Yeon Kim,Jin-Myoung Dan,So-Young Park 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-Ղ (TGF-Ղ) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-Ղ (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-Ղ in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol- induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.

지속적 복막투석 환자에서 지속되는 이차성 부갑상선 항진증에 동반된 소장의 석회화와 미만성 미세 천공에 의해 발생한 복막염 1예

차인혜 ( In Hye Cha ),조은정 ( Eun Jung Cho ),윤기철 ( Ki Chul Yoon ),홍호철 ( Ho Cheol Hong ),김혜원 ( Hye Won Kim ),양하나 ( Ha Na Yang ),김명규 ( Myung Gyu Kim ),조상경 ( Sang Kyung Jo ),김형규 ( Hyoung Kyu Kim ),조원용 ( Won Y 대한신장학회 2010 Kidney Research and Clinical Practice Vol.29 No.4

Secondary hyperparathyroidism is a common complication of chronic kidney disease and known to be associated with soft tissue calcification affecting patients` morbidity and mortality. However few cases of intestinal calcification related to secondary hyperparathyroidism have been reported. Herein we report a case of peritonitis complicating small intestinal perforation in a patient who had undergone peritoneal dialysis and had sustained hyperparathyroidism. Diffuse calcifications and perforations in small intestine were identified in abdomino-pelvic CT scan as well as in resected small intestine. Because of relapsing microperforation and resultant intra-abdominal abscess, the patient has been in fasting status depending on total parenteral nutrition for over 8 months after surgery.

Effect of Ticks, Haemaphysalis longicornis on production of proinflammatory cytokines from human monocytic THP-1 cells

Chang Ho Choi,Chang-Woo Kim,Hye-Ji Cha,Na-Eun Lee,Sang Jin Jeon,Kwang-Kyu Kim,Chi-Young Yun 한국응용곤충학회 2013 한국응용곤충학회 학술대회논문집 Vol.2013 No.10

Haemaphysalis longicornis (Hl) as members of the ixodid tick inhabits lots of grass thicket of field and mountain. Ticks are blood-feeding ectoparasites that can mediate a variety of diseases to human and animals, causing Lyme disease, Rocky Mountain spotted fever, and human monocytic ehrlichiosis. Particularly, ticks can trigger an inflammatory response representing symptoms about swelling and itching in human. The aim of this study is to investigate the effect of H. longicornis extract (HlE) on production of inflammatory cytokines and their mRNA in human monocytic THP-1 cells. In a time- and dose-dependent manner, human monocytic THP-1 cells was treated with HlE. Supernatants were analyzed for the production of cytokines using enzyme-linked immunosorbent assay (ELISA). mRNA level in the culture cells was measured by a reverse transcriptase-polymerase chain reaction (RT-PCR). As a result of this study, HlE significantly induced secretion of IL-6, IL-8, and MCP-1 in THP-1 cells. These results suggest that HlE increase the release of proteins and mRNAs level of inflammatory cytokines in THP-1 cells. HlE may play a role in contributing to inflammatory diseases through stimulation of immune cells. Further research of H. longicornis is needed to better understand the elucidation of the pathogenic mechanism.

Development of Infrastructure for the Production of Porcine Embryonic Stem Cells derived from In Vivo-Derived Blastocyst

Hye-Jin Cha,Na-Rae Han,Sang-Hee Lee,Jung-Im Yun,Eun-Song Lee,Seung-Tae Lee,Choon-Keun Park 한국동물생명공학회(구 한국동물번식학회) 2013 발생공학 국제심포지엄 및 학술대회 Vol.2013 No.1

Basic, Research : EGR1 Control the Differentiation of BM-derived Mesenchymal Stem Cells into Functional Hepatocyte through Mesenchymal-Epithelial Transition

( Hye Lim Kim ),( Si Hyun Bae ),( Jung Hoon Cha ),( Na Ri Park ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Mesenchymal-Epithelial transition (MET) in hepatic stem cells is important to multiple processes, including hepatogenic differentiation and liver development, regeneration. Early growth response (EGR) 1, transcription factor of early growth response gene family, is induced in the responses to a number of growth and differentiation factors. The aim of this study is to investigate that EGR1 acts as a key regulator of EMT/MET in the process of hepatogenic differentiation from bone marrow-derived mesenchymal stem cells (BM-MSCs). Methods: Pas staining and Urea production test were performed to verify the functionality of hepatogenic differentiation. To search for novel proteins in BM-MSCs before and after differentiation, protein/DNA array was performed. Immunohistochemistry were identified the enhanced expression of EGR1 and MET markers, accompanied by decreased expression of EMT markers. To determine the effect of EGR1, BMMSCs were infected by lenti-shEGR1. To determine the role of EGR1 in BM-MSCs which were infected by lenti-shEGR1, MET/EMT markers during the hepatogenic differentiation were identified by immunoblotting, immuno- fluorescence. Results: During differentiation proceeds, from day 1 to day 28, stem cells change in shape from spindle to polygon with larger size and tighter intercellular connections. Intracellular glycogen and urea production was significantly increased from day 1 to day 28. The mRNA expression of liver-specific genes was upregulated. In order to study key regulator in hepatogenic differentiation, we performed protein/DNA array. EGR1 in differentiated BM-MSCs were significantly increased during the culture compared to undifferentiated BM-MSCs. In contrast, downregulation of EGR1 by lenti-shRNA reduced hepatogenic differentiation and increased the expression of EMT related genes in associaton with the decreased expression of MET related gene. Conclusions: In this study, we identified novel factors in the process of hepatogenic differentiation through inducing the MET process. Our study suggests that EGR1 were expected to the “transcription factor therapy” as novel strategy in future clinical treatment.

Protective mechanism of curcumin against Vibrio vulnificus infection.

Na, Hee Sam,Cha, Mi Hye,Oh, Dool-Ri,Cho, Cheong-Weon,Rhee, Joon Haeng,Kim, Young Ran Elsevier Science Publishers, B.V. on behalf of the 2011 FEMS immunology and medical microbiology Vol.63 No.3

<P>Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., has many beneficial biological activities. However, there are relatively few reports of the effects of curcumin on pathogen infections. This study examined the effect of curcumin on a Vibrio vulnificus infection. The cytotoxicity of V. vulnificus to HeLa cells was significantly inhibited by curcumin (at 10 or 30?μM). To further examine the inhibitory mechanism of curcumin against V. vulnificus-mediated cytotoxicity, the level of bacterial growth, bacterial motility, cell adhesion, RTX toxin expression and host cell reactions were evaluated. Curcumin inhibited V. vulnificus growth in HI broth. Curcumin inhibited both bacterial adhesion and RTX toxin binding to the host cells, which can be considered the major protective mechanisms for the decrease in V. vulnificus cytotoxicity. Curcumin also inhibited host cell rounding and actin aggregation, which are the early features of cell death caused by V. vulnificus. In addition, curcumin decreased the V. vulnificus-induced NF-κB translocation in HeLa cells. Finally, curcumin protected mice from V. vulnificus-induced septicemia. In conclusion, curcumin may be an alternative antimicrobial agent against fatal bacterial infections.</P>