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>

Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

문형근,Chil Sung Kang,최준표,최동식,Hyun Il Choi,최용욱,전성규,유주연,Myoung Ho Jang,고용송,김윤근 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.1

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation,which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17positive feedback.

Phenotypic Polarization of Activated Astrocytes: The Critical Role of Lipocalin-2 in the Classical Inflammatory Activation of Astrocytes

Jang, Eunha,Kim, Jong-Heon,Lee, Shinrye,Kim, Jae-Hong,Seo, Jung-Wan,Jin, Myungwon,Lee, Maan-Gee,Jang, Il-Sung,Lee, Won-Ha,Suk, Kyoungho The American Association of Immunologists, Inc. 2013 JOURNAL OF IMMUNOLOGY Vol.191 No.10

<P>Astrocytes provide structural and functional support for neurons, as well as display neurotoxic or neuroprotective phenotypes depending upon the presence of an immune or inflammatory microenvironment. This study was undertaken to characterize multiple phenotypes of activated astrocytes and to investigate the regulatory mechanisms involved. We report that activated astrocytes in culture exhibit two functional phenotypes with respect to pro- or anti-inflammatory gene expression, glial fibrillary acidic protein expression, and neurotoxic or neuroprotective activities. The two distinct functional phenotypes of astrocytes were also demonstrated in a mouse neuroinflammation model, which showed pro- or anti-inflammatory gene expression in astrocytes following challenge with classical or alternative activation stimuli; similar results were obtained in the absence of microglia. Subsequent studies involving recombinant lipocalin-2 (LCN2) protein treatment or <I>Lcn2</I>-deficient mice indicated that the pro- or anti-inflammatory functionally polarized phenotypes of astrocytes and their intracellular signaling pathway were critically regulated by LCN2 under in vitro and in vivo conditions. Astrocyte-derived LCN2 promoted classical proinflammatory activation of astrocytes but inhibited IL-4–STAT6 signaling, a canonical pathway involved in alternative anti-inflammatory activation. Our results suggest that the secreted protein LCN2 is an autocrine modulator of the functional polarization of astrocytes in the presence of immune or inflammatory stimuli and that LCN2 could be targeted therapeutically to dampen proinflammatory astrocytic activation and related pathologies in the CNS.</P>

YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

PAENG, SUNG HWA,PARK, WON SUN,JUNG, WON-KYO,LEE, DAE-SUNG,KIM, GI-YOUNG,CHOI, YUNG HYUN,SEO, SU-KIL,JANG, WON HEE,CHOI, JUNG SIK,LEE, YOUNG-MIN,PARK, SAEGWANG,CHOI, IL-WHAN UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.36 No.3

<P>YCG063 is known as an inhibitor of reactive oxygen species?(ROS); however, its intracellular mechanisms of action remain poorly understood. In the present study, we investigated the effects of YCG063 on the inflammatory response of Pseudomonas aeruginosa lipopolysaccharide?(PA-LPS)?stimulated human retinal pigment epithelial cells?(RPE cells). Human adult RPE cells?(ARPE?19) were stimulated with PA-LPS. We then investigated the LPS-induced expression of several inflammatory mediators, such as interleukin?(IL)-6, IL-8, monocyte chemoattractant protein-1?(MCP-1) and intracellular adhesion molecule-1?(ICAM-1) in the ARPE-19 cells. We performed an enzyme-linked immunosorbent assay?(ELISA), western blot analysis, electrophoretic mobility shift assay?(EMSA) and fluorescence-activated cell sorting?(FACS) to elucidate the mechanisms involved in the anti-inflammatory effects of YCG063 in the PA-LPS-stimulated cells. The results revealed that treatment with YCG063 significantly inhibited the levels of IL-6, IL-8, MCP-1 and ICAM-1 in the PA-LPS-stimulated ARPE-19 cells. YCG063 also markedly inhibited the phosphorylation of AKT in the PA?LPS-stimulated cells. In addition, the activation of nuclear factor-κB?(NF-κB) was also attenuated folllowing treatment with YCG063. ROS were not generated in the PA-LPS-stimulated cells. In conclusion, our data indicate that YCG063 may prove to be a potential protective agent against inflammation, possibly through the downregulation of Toll?like receptor?2?(TLR2) and the AKT-dependent NF-κB activation pathway in PA-LPS-stimulated ARPE-19 cells. Furthermore, this anti-inflammatory activity occurred through ROS-independent signaling pathways.</P>

활성화된 렛트 비만세포와 마우스 소양증에 대한 한약재로 조성된 WSY-1075의 항염증 및 항소양 효과

황성연 ( Sung Yeoun Hwang ),이승호 ( Seung Ho Lee ),이가위 ( Chia Wei Lee ),김장호 ( Jang Ho Kim ),장선일 ( Seon Il Jang ),김안나 ( An Na Kim ),김홍준 ( Hong Jun Kim ) 대한본초학회 2013 大韓本草學會誌 Vol.28 No.4

Objectives : This study was to evaluate the anti-inflammatory and anti-pruritic effects of WSY-1075 composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in rat peritoneal mast cells (RPMCs) and scratching mouse model. Methods : WSY-1075 was prepared by extracting with 30% ethanol. In the present study, we investigated the effect of WSY-1075 on the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and histamine in rat peritoneal mast cells (RPMCs) activated with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187, and on the scratching behavior in mice treated with pruriogens. Results : WSY-1075 was not cytotoxic effect in used all concentration. PMA plus A23187 treatment significantly increased TNF-α, IL-1β and IL-6 production compared with media control in RPMCs. However, TNF-α, IL1β and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by WSY-1075 (200 μg/mL and 400 μg/mL). WSY-1075 also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, WSY-1075 administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin and substence P) in ICR mice. Conclusion : These results suggest that WSY-1075 administration (200 mg/kg or 400 mg/kg) has the anti-inflammatory and anti-pruritic effects on the activated rat peritoneal mast cell and mouse pruritus. WSY-1075 has a potential use as a composition of medicinal plants for treatment against inflammation- and pruritus-related disease.

Jageum-Jung, the herbal pharmaceuticals, inhibits the hepatic fibrogenesis as mediated with TGF-β1/smad signaling

송유림,Jang Mi Hee,Jang Boyun,Bae Su Jin,Bak Seon Been,Lee Sung Min,Yun Un-Jung,Lee Ju Hee,Park Sang Mi,Jung Dae Hwa,Sa Bok Suk,Song Jong Kuk,이은혜,김광연,Park Kwang-Il,김영우,김상찬 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.2

Background Herbal prescriptions have various effects and their efficacy is potentiated by the use of combinations of medicinal herbs. Objective Jageum-Jung (JGJ) is a traditional oriental medical prescription composed of five herbs. It has been used for detoxifi cation, and as an anti-inflammatory and antitumor agent. However, the effect of JGJ on hepatic fibrogenesis is unclear. Results We investigated the role of JGJ in TGF-β1/smad signaling, which is implicated in fibrogenesis, and its hepatoprotective effect in CCl 4 -treated mice with liver fi brosis. Treatment of LX-2 cells with TGF-β induced expression of mediators (α-SMA, PAI-1, and MMP-2) of fibrogenesis and activation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6). However, these were downregulated by pretreatment with JGJ. In mice, oral administration of JGJ prevented liver injury induced by CCl 4 , as indicated by decreases in the ALT and AST levels. Conclusions JGJ inhibits hepatic fibrogenesis and TGF-β1/Smad signaling.

Rosmarinic acid와 luteolin의 항염증에 대한 상승효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.1

본 연구에서는 들깨 유래 기능성 물질인 rosmarinic acid (RA)와 luteolin이 RAW264.7 세포에서 항염증작용에 대한 상승 효과가 있는지 알아보고자 하였다. 그 결과 RAW264.7 세포에 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 염증 매개 인자인 NO, iNOS, PGE2, COX-2의 생성을 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 더 뛰어나게 억제하였다. 또한 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 TNF-α, IL-6, IL-1β 같은 염증성 사이토카인의 생성량을 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 더 뛰어나게 억제하는 것을 확인하였다. 그리고 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 NF-κB의 subunit인 p65의 translocation과 IκB-α의 degradation을 더 뛰어나게 억제하는 것을 볼 수 있어 두 화합물 간의 상승작용이 뚜렷함을 확인 할 수 있었고, RA와 luteolin 두 화합물을 동시에 처리할 경우 염증관련 질환 치료에 유용하게 활용될 수 있을 것으로 판단된다. The aim of this study was to investigate the synergistic anti-inflammatory effect of rosmarinic acid (RA) and luteolin from perilla (Perilla frutescens L.) leaves in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. A combination of RA and luteolin more strongly inhibited the production of nitric oxide (NO), inducible NOS (iNOS), prostaglandin E2 (PGE2), and COX-2 than higher concentrations of RA or luteolin alone in LPS-stimulated RAW264.7 macrophages. The combined RA and luteolin synergistically inhibited the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in LPS-stimulated RAW264.7 macrophages. Furthermore, combined RA and luteolin more strongly suppressed NF-κB activation than RA or luteolin alone, by inhibiting the degradation of inhibitor of NF-κB (IκB)-α and nuclear translocation of the p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Collectively, these results suggest that RA and luteolin in combination exhibit synergistic effects in suppression of LPS-induced inflammation in RAW264.7 macrophages.

CagL 재조합 단백질 접종후에 Mongolian gerbil에서 나타나는 Helicobacter pylori 감염에 대한 반응

박은정,장성일,최윤희,김진문,김애련,김지혜,우계형,유윤정,이성행,차정헌,Bak, Eun-Jung,Jang, Sung-Il,Choi, Yun-Hui,Kim, Jin-Moon,Kim, Ae-Ryun,Kim, Ji-Hye,Woo, Gye-Hyeong,Yoo, Yun-Jung,Lee, Sung-Haeng,Cha, Jeong-Heon 한국미생물학회 2012 미생물학회지 Vol.48 No.2

Helicobacter pylori는 만성 위염, 소화성 궤양, 위암의 중요한 역학적 인자중 하나이다. H. pylori의 독성인자중 CagL은 숙주 세포와 H. pylori의 제 4형 분비기관(Type 4 secretion system)을 연결하는 adhesin으로 작용하는 섬모 단백질로 H. pylori가 발병하는데 중요한 역할을 하는 것으로 알려져 있다. 이번 연구는 저빌에 H. pylori를 감염시킨 동물 모델을 이용하여 CagL 재조합 단백질을 면역화시켰을 때 나타나는 효과를 평가하였다. 재조합 CagL은 클론되었고, 과발현시켜 정제하여 준비하였다 저빌은 H. pylori 감염 대조군과 H. pylori 감염 CagL 재조합 단백질 접종군으로 분류하였고, 접종시 알루미늄 애쥬번트를 사용하였다. 일주일 간격으로 4회 근육내 접종하였고, 마지막 접종 일주일 후, 모든 저빌에 H. pylori 7.13 균주를 $1{\times}10^9\;bacteria/500{\mu}l$ 농도로 위내 투여하였다. H. pylori 감염 6주째 모든 저빌을 희생하여 혈청 IgG 반응평가를 위한 ELISA를 실시하였고, 위에서는 집락화된 H. pylori의 수평가, 병리조직학적 평가 및 사이토카인 유전자발현을 조사하였다. CagL 재조합 단백질접종 일주일 후부터 H. pylori 감염 CagL 재조합 단백질 접종군의 혈청내 IgG 항체형성이 유의적으로 증가하였다. 위에서의 집락화된 세균수는 두군의 차이가 없었다. 저빌 체중에 대한 위무게 비율는 H. pylori 감염 CagL 재조합 단백질 접종군이 유의적으로 감소하였으나 병리조직학적 평가에서는 유의적인 차이는 확인하지 못하였다. 위에서의 IL-$1{\beta}$와 KC (IL-8 homologues)의 유전자발현 정도도 두 군사이에 유의적인 차이는 없었다. 이번 결과는 CagL 재조합 단백질의 접종은 IgG 항체형성은 효과적으로 자극하였지만 면역화된 숙주에서 세균 집락화의 감소 및 병변형성의 방어까지는 유도하지 못한 것으로 나타났으며, 앞으로 H. pylori 감염에 대해 유효한 면역 반응 및 질병 방어 효과를 나타내기 위해서 CagL을 포함한 다른 종류의 재조합 항원 사용 및 보조적으로 전신 면역 및 점막 면역을 효과적으로 유도하기 위해 안정성있는 애쥬번트의 사용을 고려해야 할 것으로 사료된다. Helicobacter pylori is an important factor of chronic gastritis, digestive ulcer, and stomach cancer. CagL, a virulence factor of H. pylori, is well-known as a pilus protein which acts as adhesion to host cell and a component of Type 4 secretion system. In this study, we evaluated the protective response of recombinant CagL protein (rCagL) using Mongolian gerbil animal model for H. pylori infection. The cagL gene was cloned from 26695 H. pylori followed by over-expression and purification of the protein in E. coli. Mongolian gerbils were immunized with rCagL protein mixed with aluminum adjuvant via intramuscular injections once a week during 4 weeks. At a week after the last immunization, the Mongolian gerbils were administrated with H. pylori 7.13 strain into the stomach and sacrificed to measure antibody titer on rCagL by ELISA and bacterial colonization in the stomach, and to examine the histopathological changes and cytokine expression at 6 week after challenge. Antibody titers on recombinant protein were significantly increased from a week after the first immunization. There was no significant change of the number of bacterial colony between control group and immunized group. The relative stomach weight was significantly decreased in immunized group, but the significant change of histopathological assessment was not observed in the stomach. Cytokine expression such as IL-$1{\beta}$ and KC also was not significantly different between control and immunized groups. These results indicate that rCagL could effectively induce the formation of the specific IgG antibodies. However, bacterial colonization and histopathological lesions could not be inhibited by the immunization in the stomach, indicating not enough protection against H. pylori infection. We consider that along with CagL other adequate antigens could be needed stimulating immune response and inducing protective effects against gastric disease, and also a better adjuvant could be considered.

마우스 복강대식세포에서 가감공진단(加減拱辰丹)의 항염증 효과

김홍준,김영식,목지예,정승일,황성연,조정근,장선일,Kim, Hong-Jun,Kim, Young-Sik,Mok, Ji-Ye,Jeong, Seung-Il,Hwang, Sung-Yeoun,Cho, Jung-Keun,Jang, Seon-Il 대한한의학방제학회 2011 大韓韓醫學方劑學會誌 Vol.19 No.1

Objectives : In a previous study, we have shown that Gagam-Gongjin-Dan(GGD) has an inhibitory effect on the ovalbumin-induced immune responses and a hepatoprotective effect on actaminophen-induced liver injury in Balb/c Mice. However, the possible anti-inflammatory effect of GGD extract for inflammatory mediators was not reported. Therefore, the purpose of this study was to investigate an inhibitory effects of GGD extract against lipopolysaccharides(LPS) induced inflammatory mediators in mouse peritoneal macrophages. Methods : GGD extract was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Accumulated nitrite, an oxidative product of nitric oxide(NO), was measured in the culture medium by the Griess reaction. The levels of prostaglandin $E_2(PGE_2)$, interleukin-$1{\beta}$(IL-$1{\beta}$), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) were measured by Western blot analysis. Results : GGD extract (50-$400\;{\mu}g$/ml) per se had no cytotoxic effect in LPS-stimulated peritoneal macrophages. GGD extract dose-dependently reduced NO, $PGE_2$, IL-$1{\beta}$ and TNF-${\alpha}$ production and COX-2 activity caused by stimulation of LPS. The levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with GGD extract in a dose dependent manner. Conclusions : These results suggest that GGD extract has an anti-inflammatory effect against LPS-induced inflammatory mediators in peritoneal macrophages, these properties may contribute to inflammation disease care.

Solar Cells: Amorphous Zinc Stannate (Zn₂SnO₄) Nanofibers Networks as Photoelectrodes for Organic Dye‐Sensitized Solar Cells (Adv. Funct. Mater. 25/2013)

Choi, Seung‐,Hoon,Hwang, Daesub,Kim, Dong‐,Young,Kervella, Yann,Maldivi, Pascale,Jang, Sung‐,Yeon,Demadrille, Renaud,Kim, Il‐,Doo WILEY‐VCH Verlag 2013 Advanced Functional Materials Vol.23 No.25

<P>Highly porous amorphous Zn<SUB>2</SUB>SnO<SUB>4</SUB> electrodes are prepared using electrospinning techniques and combined with organic or ruthenium dyes to fabricate dye‐sensitized solar cells. As reported by Sung‐Yeon Jang, Renaud Demadrille, Il‐Doo Kim, and co‐workers on page 3146, the devices based on 3‐μm‐thick electrodes and the organic dyes demonstrate significantly improved performances compared to those using the ruthenium complex. Using this approach, solar cells with power conversion efficiencies up to 3.7% are obtained. </P>