The enhanced IL-l8 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT)

Cho, Daeho,Kang, Jae Seung,Park, Jong Hoon,Kim, Young-In,Hahm, Eunsil,Lee, Junechul,Yang, Yoolhee,Jeon, Junho,Song, HyunKeun,Park, Hyunjeong,Kim, Taesung,Pang, Saic,Kim, Chul-Woo,Hwang, Young Il,Lee, 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Based on our recent observation that enhanced IL-18 expression positively correlates with malignant skin tumors, such as SCC and melanoma, we examined the possible role of UVB, known to be associated with skin cancer development, in the enhancement of IL-18 production using primary human epidermal keratinocytes and human cell line HaCaT. After cells were exposed to UVB irradiation in vitro, IL-18 production was examined by Northern blot analysis and ELISA, and it was found that IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by antioxidant, N-acetyl-ι-cysteine (NAC), which suggested the involvement of reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced IL-18 synthesis. We also found that UVB irradiation increased AP-1 binding activity by using EMSA with AP-1-specific oligonucleotide. Furthermore, inhibitors of UVB-induced AP-1 activity, such as PD98059, blocked enhanced IL-18 production, indicating that AP-1 activation is required for UVB-induced IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced IL-18 production is selectively mediated through the generation of ROI and the activation of AP-1.

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.

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>

Regulation of interleukin-11 expression in ovulatory follicles of the rat ovary

Jang, You-Jee,Park, Jae-Il,Jeong, Seong-Eun,Seo, You-Mi,Dam, Phuong T. M.,Seo, Young-Woo,Choi, Bum-Chae,Song, Sang-Jin,Chun, Sang-Young,Cho, Moon-Kyoung Commonwealth Scientific and Industrial Research Or 2017 Reproduction, fertility, and development Vol. No.

<P> The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6 h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression. IL-11 protein expression was stimulated in theca cells by hCG. LH-stimulated increases in Il11 mRNA levels in cultured preovulatory follicles were inhibited by protein kinase A and mitogen-activated protein kinase kinase inhibitors. Toll-like receptor (TLR) 2 and TLR4 were detected in preovulatory follicles, and the TLR4 ligand lipopolysaccharide, but not the TLR2 ligand Pam3Cys, increased Il11 mRNA levels in theca cells, but not in granulosa cells. Treatment of preovulatory follicles with IL-11 stimulated progesterone production and steroidogenic acute regulatory protein (Star) gene expression. Together, these results indicate that IL-11 in theca cells is stimulated by mitogen-activated protein kinase signalling and TLR4 activation, and increases progesterone production during ovulation. </P>

감껍질 열수 및 초임계 유체 추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),신재영(Jae Young Shin),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.3

본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Min Jin-Young,Kim Jin Youp,성충만,Kim Seon Tae,조현진,문수진,Cho Sung-Woo,Hong Sang Duk,Ryu Gwanghui,Cho Kyoung Rai,Kim Young Hyo,Park Soo-Kyoung,Kim Dong-Kyu,Lee Dong Hoon,Heo Sung Jae,Lee Ki-Il,Kim Su Jin,Le 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.4

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

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

Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-α gene promoter polymorphisms

Cheong, Jae Youn,Cho, Sung Won,Hwang, Il Lan,Yoon, Seung Kew,Lee, June Hyuk,Park, Choon Sik,Lee, Jong Eun,Hahm, Ki Baik,Kim, Jin Hong Blackwell Publishing Asia 2006 Journal of gastroenterology and hepatology Vol.21 No.7

<P>Abstract</P><P>Background: </P><P>The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-α and interleukin(IL)-10 gene promoter.</P><P>Methods: </P><P>A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 witih chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (−1082, −819, −592), and TNF-α gene promoter (−308, −238) were assessed by single base primer extension assay.</P><P>Results: </P><P>The frequency of C/C genotype at position −592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, <I>P</I> = 0.036). The IL-10 gene promoter −592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (<I>P</I> = 0.003). Genotype frequencies of TNF-α gene promoter at position −308 and −238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, −308G/−238G homozygotes were associated with HBV persistence (<I>P</I> = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease.</P><P>Conclusions: </P><P>The carriers of the −592A allele in the IL-10 promoter and −308G/−238G haplotype homozygotes in the TNF-α promoter region have higher risk of persistent HBV infection.</P>

Soybean Fermented with Bacillus amyloliquefaciens (Cheonggukjang) Ameliorates Atopic Dermatitis-Like Skin Lesion in Mice by Suppressing Infiltration of Mast Cells and Production of IL-31 Cytokine

( Byoung Ok Cho ),( Jae Young Shin ),( Ji-su Kim ),( Denis Nchang Che ),( Hyun Ju Kang ),( Do-youn Jeong ),( Seon Il Jang ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.5

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as NF-κB and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

2,3-Dehydrosilybin Suppresses IL-31-Associated Pruritus Factors in Astrocytes and Microglia

Ji Hyeon Park,Jae Young Shin,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang,Byoung Ok Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Chronic pruritus is the main symptom that increases the suffering of patients in hypersensitivity disorder disease. IL-31 is a pruritic cytokine with a primary objective to control itch. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. This study investigated the effect of DHS pretreatment on IL-31-associated pruritus in astrocytes and microglia. Pretreatment with DHS inhibited the production of IL-31 by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) stimulation in microglia. Pretreatment with DHS inhibited the phosphorylation of MAPK, STAT1 and NF-κB by LPS plus IFN-γ stimulation in microglia. In addition, DHS suppressed the expression of IL-31 receptor A in IL-31-treated astrocytes. DHS also inhibited lipocalin2 production in IL-31 stimulated astrocytes. Taken together, DHS has potential as a therapeutic agent for symptom relief by down-regulating the IL-31-mediated pruritus mechanism in microglia and astrocytes.