Activation of Transient Receptor Potential Melastatin Family Member 8 (TRPM8) Receptors Induces Proinflammatory Cytokine Expressions in Bronchial Epithelial Cells

김주희,Young Sook Jang,Hwan Il Kim,박지영,박성훈,Yong Il Hwang,Seung Hun Jang,Ki-Suck Jung,Hae Sim Park,Choon-Sik Park 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions: TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

퇴행성 관절염에서 Interleukin-6와 Soluble Interleukin-6 Receptor

장재석 ( Jae Suk Chang ),정용갑 ( Yong Gab Jeong ),조우신 ( Woo Shin Cho ),빈성일 ( Seong Il Bin ),엄규황 ( Kyu Hwang Ym ),김정화 ( Jung Hwa Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.3

Objective: Unlike other soluble receptors, the soluble interleukin-6 receptor (sIL-6R) cooperates with IL-6 to activate gp130 of effector cell. As the IL-6 and sIL-6R are important in the rheumatoid disease, this study was designed to measure concentration of IL-6 and sIL-6R in synovium and synovial fluid of the degenerative arthritis. Methods: The synovium and synovial fluid were obtained during total knee replacement arthroplasty. The synovium was taken from eleven patients, and synovial fluid taken from sixteen patients. Same patients between two groups were seven. Tissue cultures of the synovial tissues were done with 10% FBS for 72 hours. After irrigation, thery were incubated for 48 hours without FBS, and the culture media and the synovial fluid were collected after centrifuged at 2500rpm for 10 minutes. The level of IL-6 and sIL-6R were measured by quantitative sandwich enzyme immunoassay technique. Results: In the synovium, the IL-6 level was 5.1±0.12ng/ml, and the sIL-6R level was 0.41±0.25ng/ml. In the synovial fluid, the IL-6 level was 0.09± 0.15ng/ml, and the sIL-6R level was 10.37±3.28ng/ml. These results show that IL-6 concentration was measured highly in two groups, especially in synovium (sixty times), and the sIL-6R concentration was measured significantly high in synovial fluid (twenty-five times). Conclusion: The IL-6 and sIL-6R were elevated in degenerative arthrits. We confirmed the source of IL-6 was synovium (very high in synovial tissue culture media), but we need further study for the source of sIL-6R as it was remarkably elevated as IL-6 and its level was lower than serum.

Corrigendum to “Vertebral Body Anterior Translation, a Novel Technique for Delayed Myelopathy Due to Osteoporotic Spine Fractures”

Jung Soo Lee,Dong Ki Ahn,Won Shick Shin,Kyung Jun Cho,Young Rok Ko,Il Chan Hwang 대한정형외과학회 2022 Clinics in Orthopedic Surgery Vol.14 No.4

Clinics in Orthopedic Surgery 2020;12:485-492 https://doi.org/10.4055/cios20028 In the article entitled “Vertebral body anterior translation, a novel technique for delayed myelopathy due to osteoporotic spine fractures,”1) the name of one of the authors was incorrectly presented: Il Chan Whang should read Il Chan Hwang.

The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis

Jung, Joo Hyun,Kang, Il Gyu,Kim, Dae Young,Hwang, You Jin,Kim, Seon Tae The Korean Society of Ginseng 2013 Journal of Ginseng Research Vol.37 No.2

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL-5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.

Effects of Chung-Pae Inhalation Therapy on a Mouse Model of Chronic Obstructive Pulmonary Disease

Hwang, Joon-Ho,Lee, Beom-Joon,Jung, Hee Jae,Kim, Kwan-Il,Choi, Jun-Yong,Joo, Myungsoo,Jung, Sung-Ki Hindawi Publishing Corporation 2015 Evidence-based Complementary and Alternative Medic Vol.2015 No.-

<P>Chung-pae (CP) inhalation therapy is a method frequently used in Korea to treat lung disease, especially chronic obstructive pulmonary disease (COPD). This study investigated the effects of CP inhalation on a COPD animal model. C57BL/6 mice received porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) alternately three times for 3 weeks to induce COPD. Then, CP (5 or 20 mg/kg) was administered every 2 h after the final LPS administration. The effect of CP was evaluated by bronchoalveolar lavage (BAL) fluid analysis, histological analysis of lung tissue, and reverse transcription polymerase chain reaction analysis of mRNA of interleukin- (IL-) 1<I>β</I>, tumor necrosis factor- (TNF-) <I>α</I>, IL-6, and tumor growth factor- (TGF-) <I>β</I>. Intratracheal CP administration reduced the number of leukocytes and neutrophils in BAL fluid, inhibited the histological appearance of lung damage, and decreased the mRNA levels of the proinflammatory cytokines IL-1<I>β</I>, TNF-<I>α</I>, IL-6, and TGF-<I>β</I>. Intratracheal CP administration effectively decreased the chronic inflammation and pathological changes in a PPE- and LPS-induced COPD mouse model. Therefore, we suggest that CP is a promising strategy for COPD.</P>

식육중 잔류항균물질 비교 조사 -서울지역 도축 소와 돼지를 중심으로-

변정옥 ( Jung Ok Byun ),강영일 ( Young Il Kang ),이달주 ( Dal Ju Lee ),황래홍 ( Lae Hong Hwang ),이양수 ( Yang Soo Lee ),이병동 ( Byung Dong Lee ) 한국동물위생학회 2002 한국동물위생학회지 (KOJVS) Vol.25 No.3

This study was carried out to compare the residual antibiotic materials in muscles of slaughter cattle and swine from slaughterhouses in Seoul from 2000 to 2001 by EEC-4-plate method, Charm Il and HPLC method. 1. Residual antibiotic materials were detected from 95 samples(0.8%) by EEC-4-plate and 57 samples(10.2%) by Charm Il. The final HPLC method determined the positives are 43(45.3%) and 27(47.3%) respectively. 2. The detection ratios were 45% by EEC-4-plate and 47% by Charm Il. 3. Seventy samples were classified as tetracyclines 56(75.7.4%), sulfonamides 10(14.9%), β-lactam 6(8.1%) chloramphenicol 1(1.4%). Three of them were confirmed to be positive simmultaneously for tetracyclines, sulfonamides and chloramphenicol. 4. The highest residual concentration of chlortetracycline, oxytetracycline, sulfamethazine, sulfadimethoxine, sulfaquinoxaline, penicillin, ampicillin and chloramphenicol were 0.34, 11.29, 68.16, 0.13, 4.0, 0.12, 0.4 and 0.04ppm, respectively.

The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis

Joo Hyun Jung,Il Gyu Kang,Dae Young Kim,You Jin Hwang,Seon Tae Kim 고려인삼학회 2013 Journal of Ginseng Research Vol.37 No.2

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL-5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.

Regulation of UVB-Induced IL-8 and MCP-1 Production in Skin Keratinocytes by Increasing Vitamin C Uptake via the Redistribution of SVCT-1 from the Cytosol to the Membrane

Kang, Jae Seung,Kim, Ha Na,Jung, Da Jung,Kim, Jee Eun,Mun, Ga Hee,Kim, Yeong Seok,Cho, Daeho,Shin, Dong Hoon,Hwang, Young-Il,Lee, Wang Jae Williams & Wilkins 2007 The Journal of investigative dermatology Vol.127 No.3

It is well known that UVB (290–320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.Journal of Investigative Dermatology (2007) 127, 698–706. doi:10.1038/sj.jid.5700572; published online 28 September 2006

가감목방기탕(加減木防己湯)이 흰쥐의 Adjuvant 유발 관절염에 미치는 영향

황덕순,김순중,서일복,Hwang, Duk-Soon,Kim, Sun-Jung,Seo, Il-Bok 대한한의정보학회 2005 大韓韓醫情報學會誌 Vol.11 No.1

Objectives : This study was to investigate the effect of Kagammokbanggi-tang on the Freund's Complete Adjuvant(FCA)-induced arthritis in rats. Methods : Arthritis was induced by intradermal injection of FCA into base of tail. Arthritic rats were divided into control(n=10) and sample(n=10) group. Control group was taken normal saline for twenty days and sample group was taken extracts of Kagammokbanggi-tang for same duration. Normal group(n=10), non-arthritic group, was injected with mineral oil and was taken normal saline for twenty days. Body weight, paw edema volume and ankle joint thickness were measured at 0, 10, 15, 20 days after treatment. $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, $PGE_2$ in synovia were analysed by ELISA at 20 days after treatment. Histochemical investigation of NADPH-d in the PAG and histopathological study on the ankle joint were performed at 20 days after treatment. Results : Paw edema volume, ankle joint thickness, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, $PGE_2$, NADPH-d of sample group were significantly decreased compared with control group. Conclusions : These results indicated that Kagammokbanggi-tang has antiarthritic and analgesic effects, and inhibited expression of NOS on the progression of FCA- induced arthritis in rats.

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>