Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.

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.

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>

Elderly kidney transplant recipients have favorable outcomes but increased infection-related mortality

임정훈,Lee Ga Young,Jeon Yena,Jung Hee-Yeon,Choi Ji Young,CHO, JANG-HEE,Park Sun Hee,김용림,Kim Hyung-Kee,Huh Seung,유은상,Won Dong Il,Kim Chan-Duck 대한신장학회 2022 Kidney Research and Clinical Practice Vol.41 No.3

Background: The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

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.

(2S)-2′-Methoxykurarinone from Sophora flavescens Suppresses Cutaneous T Cell-Attracting Chemokine/CCL27 Expression Induced by Interleukin-β/Tumor Necrosis Factor-α via Heme Oxygenase-1 in Human Keratinocytes

Seung-Il Jeong,Young-Eun Lee,Seon Il Jang 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.5

One of the CC chemokines, cutaneous T cell-attracting chemokine (CTACK/CCL27), is a skin-specific CC chemokine that is produced constitutively by keratinocytes and is highly up-regulated in inflammatory skin conditions such as atopic dermatitis and contact dermatitis. (2S)-2′-Methoxykurarinone (MOK) from Sophora flavescens has been demonstrated to have antioxidant effects. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. This study aimed to define whether and how MOK regulates skin specific CTACK/CCL27 chemokine production in human HaCaT keratinocytes. The level of CTACK/CCL27 and HO-1 expression was measured by reverse transcription-polymerase chain reaction, and signaling was evaluated by western blot analysis. CTACK/CCL27 production was determined by enzyme-linked immunosorbent assay. Pretreatment with MOK suppressed tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced CTACK/CCL27 production in human HaCaT keratinocytes. MOK inhibited TNF-α- and IL-1β-induced nuclear factor κB (NF-κB) activation. Interestingly, pretreatment with MOK significantly suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production through the induction of HO-1. This suppression was completely abolished by HO-1 small interfering RNA. Furthermore, carbon monoxide, but not other end products of HO-1 activity, also suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production. These results demonstrate that MOK attenuates TNF-α- and IL-1β-induced production of CTACK/CCL27 in human HaCaT keratinocytes by inhibiting NF-κB activation and induction of HO-1.

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.

$CD4^+$ Jurkat T 세포주에서 Th1과 Th2 사이토가인 조절에 미치는 황금 유래 Baicalin, Baicalein 및 Wogonin의 효과

김용준,이정치,김홍용,설광화,윤용갑,장선일,Kim Young Jun,Lee Jeong Chi,Kim Hong Yong,Xie Guanghua,Yun Yong Gab,Jang Seon Il 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.3

In the present study, baicalin, baicalein, and wogonin, a major flavone isolated from Scutellaria Radix were examined for their effects on PMA-induced Interlukin-6 (IL-6), $interferon-\gamma(IFN-\gamma)$, tumor necrosis factor $(TNF)-\alpha$, IL-4, IL-10, and IL-13 productions in the PMA-stimulated $CD4^+$ Jurkat T cells. These three compounds inhibited PMA-induced Th1 cytokine $(IL-6,\;IFN-\gamma,\;TNF-\alpha)$ and Th2 cytokine (IL-4 and IL-13) productions in a concentration-dependent manner. But wogonin, but not baicalin baicalein, increased PMA-induced IL-10 production. These results suggest that baicalin, baicalein, and wogonin, a major flavone modulate Th1 and Th2 cytokine productions in $CD4^+$ Jurkat T cells and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

고욤잎, 감잎 및 뽕잎 복합추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),신재영(Jae Young Shin),방숭주(Chong Zhou Fang),체 데니스 창(Chong Zhou Fang),장선일(Seon Il Jang) 한국식품영양과학회 2016 한국식품영양과학회지 Vol.45 No.4

본 연구는 고욤잎, 감잎 및 뽕잎을 단독으로 사용하기보다 혼합하여 사용할 경우 고욤잎, 감잎 및 뽕잎 복합추출물이 아토피 피부염(AD) 증상을 억제하는지 효과를 밝히고, 항염효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 건조 상태, 스케일링, 미란, 찰과상 및 홍반 같은 아토피 피부염 증상이 AD 모델에서 증가하였지만, 고욤잎, 감잎 및 뽕잎 각각의 추출물과 복합추출물을 투여하였을 경우 완화되는 것을 확인할 수 있었으며, 복합추출물이 고욤잎, 감잎 및 뽕잎 각각의 추출물보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증세포 및 비만세포의 침윤은 AD 모델에서 크게 증가하였지만, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어난 효과를 나타내었다. 혈청중의 IgE와 IL-4의 수치를 측정한 결과 AD 모델에서 많이 증가하였으나, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 효과를 나타내었다. HMC-1 세포에 복합추출물을 처리하였을 경우 염증성 사이토카인인 TNF-α와 IL-6의 생성량이 유의적으로 감소하였으며, 또한 RAW 264.7 세포에 복합추출물을 처리하였을 경우 염증 매개 인자인 TNF-α, IL-6, PGE2 및 NO 생성량이 감소하였고, 이러한 염증 매개 인자 억제 효능은 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 것을 확인하였다. 이러한 결과로 미루어볼 때 고욤잎, 감잎 및 뽕잎을 혼합한 복합추출물을 사용할 때 효능이 더 우수한 것을 확인하였고, 아토피 피부염 증상 개선 및 염증관련 질환 치료를 위한 기능성 천연물 소재 및 제품 개발에 응용이 가능할 것으로 생각한다. The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor (TNF)-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-${\gamma}$ Plus LPS

Jang Seon Il,Kim Young-Jun,Lee Woo-Yiel,Kwak Kyung Chell,Baek Seung Hwa,Kwak Gyu Beum,Yun Young-Gab,Kwon Tae-Oh,Chung Hun Taeg,Chai Kyu-Yun The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.2

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.