Up - Regulation of Interleukin - 4 Receptor Expression by Interleukin - 4 and CD40 Ligation via Tyrosine Kinase - Dependent Pathway

( Hyun Il Kim,Eui Young So,Suk Ran Yoon,Mi Young Han,Choong Eun Lee ) 생화학분자생물학회 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young,Lee, Choong-Eun Korean Society for Biochemistry and Molecular Biol 1998 Journal of biochemistry and molecular biology Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Lee, Choong-Eun,Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young The Korea Science and Technology Center 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

Ginsenoside Rg1 enhances CD4^(+) T-cell activities and modulates Th1/Th2 differentiation

Lee, Eui-joon,Ko, Eunjung,Lee, Jinwoo,Rho, Samwoong,Ko, Seonggyu,Shin, Min-Kyu,Min, Byung-il,Hong, Moo-Chang,Kim, Si-young,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper(Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4 T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4^(+) T cells, but augmented CD4^(-) T-cell proliferation upon activation with anti-CD3/anti-CD28 autibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4^(-) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4^(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4^(+) T cells under Th2 skewed condition, while decreasing IFN-ysecretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naive CD4^(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4^(-) T-cell activity, as well as the correction of Th1-dominant pathological disorders.

UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

Minjung Chae,Eui-dong Son,Il-Hong Bae,조은경,Hyoung-June KIM,Ji-Yong Jung 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

The Immunoregulatory Activity of Chrysanthemum zawadskii Herbich var. latilobum-Derived Polysaccharides as a Potential Adjuvant Candidate for DC-Based Cancer Vaccines

Eui-Baek Byun,Jeong Moo Han,Kwang-Il Kim 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Dendritic cells (DCs) as professional antigen-presenting cells are used to assess adjuvants, in particular the evaluation the adjuvant selection of various vaccine platforms. Polysaccharides derived from Chrysanthemum zawadskii Herbich var. latilobum leaves (CP) was to demonstrate the immunostimulatory effect and assess its potent vaccine djuvant candidate. Results showed that CP induced maturation of the dendritic cells (DCs). In addition, CP-treated DCs activated naïve T cells to polarized CD4+ and CD8+ T cells and substantially induced the production of IFN-γ and IL-2 in vitro. Furthermore, CP initiated the maturation of DCs via the activation of MAPK and NF-κB signaling pathways. Interestingly, systemic administration of CP-treated DCs pulsed with ovalbumin (OVA) peptides significantly enhanced the immune response in vivo, which included the generation of antigen (OVA)-specific polyfunctional T cells, increased cytotoxic T lymphocyte activity, induction of Th1-mediated humoral immunity, and suppression of tumor growth. From these results, our study provided the evidence of immunostimulatory effects of CP as well as its potent vaccine adjuvant candidate.

A hydroxymethoxyl Chrysin Analogue, confers Tolerogenic Properties in Bone Marrow-Derived Dendritic Cells

Eui-Baek Byun,Jeong Moo Han,Kwang-Il Kim 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Chrysin is a major flavonoid of propolis that possesses physiological activities. We previously found a hydroxymethoxyl analogue on C4 of chrysin (CM) from gamma-irradiated chrysin. In this study, to examine whether CM has better potential as an anti-inflammatory candidate than chrysin, water solubility and anti-inflammatory activity of CM were investigated. CM showed the enhanced water solubility and lower cytotoxicity in bone marrow-derived dendritic cells (BMDCs) compared with original chrysin. CM exhibited the great anti-inflammatory activities in LPS-treated BMDCs, as demonstrated by the decreased level of pro-inflammatory cytokines (TNF-α and IL-12p70), surface molecules (CD80, CD86, MHC-I, and MHC-II), antigen-presenting ability. Furthermore, CM led to tolerogenic phenotype of BMDCs in the presence of LPS by increasing expression of indoleamine 2,3-dioxygenase-1, which is due to JNK and p38 activation. Subsequently, CM-treated BMDCs inhibited the proliferation and activation of CD4+ and CD8+ T cells while increased CD4+CD25+Foxp3+ regulatory T cells. Collectively, these results indicated that CM can be an attractive candidate of anti-inflammatory drug.

방사선조사와 저칼슘식이가 치아형성시 Interleukin-1의 분포에 미치는 영향에 관한 연구

김일중,황의환,이상래 대한구강악안면방사선학회 2000 Imaging Science in Dentistry Vol.30 No.3

Purpose : To elucidate the effects of the irradiation and calcium-deficient diet on expression of interleukin (IL)-1 during tooth formation of rat molar Materials and Methods : The pregnant three-week-old Spague-Dawley rats were used for the study. The control group was non-irradiation/normal diet group, and the experimental groups were irradiation/normal diet group and irradiation/calcium-deficient diet group . The abdomen of the rats on the 9th day of pregnancy were irradiated with single dose of 350 cGy. The rat pups were sacrificed on the 14th day after delivery and the maxillae tooth germs were taken. The specimen were prepared to make sections for light microscopy, and some of tissue sections were stained immunohistochemically with anti-IL-1 antibody. Results : In the irradiation/normal diet group, dental follicle showed fewer blood vessels, mononuclear cells, and fusions of mononuclear cells than in non-irradiation/normal diet group. Alveolar bone showed a few osteoblasts and osteoclasts. Periodontal ligament showed collagen fibers and fibroblasts with irregularity. Weak immunoreactivity for IL-1 was shown in dental follicle, alveolar bone, and periodontal ligament, In the irradiation/calcium-deficient diet group, dental follicle showed sparse cellularity. Alveolar bone showed diminished number of osteoblasts. Periodontal ligament showed irregular collagen fibers and atrophy of cementoblasts and fibroblasts. No immunore-activity for IL-1 was shown in dental follicle, alveolar bone, and periodontal ligament. Conclusion : Irradiation and calcium-deficient diet seems to cause disturbance of the expression of interleukin-1 during tooth formation of rat molar. (Korean J Oral Maxillofac Radiol 2000; 30: 159-168)

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구 ( Il Gu Kim ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현,이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.1

Objectives and methods: The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results: 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of Gr-1+ /CD11b+, CCR3+, CD4+, CD3e+/CD69+, IgE+/B220+ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of CD8+ cells in the lungs of the mice group treated with AHCR-HA didn`t show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion: We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

Streptococcus dysgalactiae로부터 분리된 히알루론산과 황화된 유도체의 구조와 항염증 활성

홍창일(Chang-Il Hong),정의길(Eui-Gil Jung),한국일(Kook-Il Han),김용현(Yong Hyun Kim),이성희(Sung Hee Lee),이홍섭(Hong Sub Lee),한만덕(Man-Deuk Han) 한국생명과학회 2016 생명과학회지 Vol.26 No.5

히알루론산(HA, Hyaluronic acid)은 β-1, 3-N-acetyl glucosamine과 β-1, 4-glucuronic acid가 반복된 선형 폴리머 고분자로서 생물학적 활성 및 생체친화성 특성 때문에 의약 및 약학분야에서 중요한 분자로 여겨지고 있다. 본 연구는 HA을 S. dysgalactiae으로 얻고, 화학적 방법을 통해 황화된 히알루론산(S-HA, Sulfated hyaluronic acid)유도체를 합성하여 그 구조와 항염증 활성을 비교하였다. HA의 생산은 S. dysgalactiae를 5 l 생물반응기를 이용하여 대량 배양하여 수용성 히알루론산(HA-WS, water soluble hyaluronic acid)과 비수용성 히알루론산(HA-WI, water insoluble hyaluronic acid)을 분리 정제하였다. 특히 HA-WI를 황화시켜 황화된 히알루론산(S-HA) 유도체를 합성하였으며, 그 수율은 90%로 나타났다. 합성된 S-HA의 구조를 FT-IR 및 ¹H/<SUP>13</SUP>C-NMR를 통해 S. dysgalactiae 로부터 생산된 표준 HA, HA-WS 및 HA-WI와 비교 분석한 결과, 황으로 치환된 양상을 확인하였다. 또한, S-HA의 항염증 활성을 RAW 264.7 대식세포를 통해 확인한 결과, S-HA는 천연 형태의 HA (HA, HA-WS)보다 nitric oxide (NO)와 COX-2 및 PGE₂ 유전자 발현이 유의하게 낮게 발현되었다. 염증 매개 cytokine인 TNF-α (<80 pg/ml) 및 IL-6 (<100 pg/ml)의 생성도 S-HA가 천연 HA보다 낮은 수준으로 정량되었다. 이 같은 결과에서 황화된 S-HA은 천연 히알루론산보다 용해성이 우수하고 염증관련 사이토카인의 생성 억제를 통해 항염증 효과를 나타내므로 염증치료제, 성형 및 생체 적용 약물전달 소재로 그 활용이 기대된다. Hyaluronic acid (HA) is an important macromolecule in medical and pharmaceutical fields. HA is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid. This work aimed to confirm the structural characteristics and anti-inflammatory activities of HA and its chemically sulfated-HA. HA was produced from a fed-batch fermentation process using Streptococcus dysgalactiae in a 5 l bioreactor. HA was isolated water-soluble form (HA-WS) and water-insoluble form (HA-WI) from culture medium, and was obtained chemically sulfated-derivative (S-HA) that resulted in a 90% yield from HA-WI. The structural features of the sulfated- HA (S-HA) were investigated by FT-IR and ¹H-NMR spectroscopy. The FT-IR and NMR patterns revealed the similarity in both the FTIR spectrum as well as NMR spectrum of both reference standard and purified HA from S. dysgalactiae. The anti-inflammatory activities of HA and S-HA were examined on LPS-induced RAW 264.7 cells. S-HA was significantly inhibited production of pro-inflammatory mediators such as nitric oxide (NO) and PGE₂ and the gene levels of iNOS and COX-2, which are responsible for the production of NO and PGE₂, respectively. Furthermore, S-HA also suppressed the overproduction of pro-inflammatory cytokine TNF-α (<80 pg/ml) and IL-6 (<100 pg/ml) compared to that of HA-WI. The present study clearly demonstrates that HA-S exhibits anti-inflammatory activities in RAW 264.7 macrophage cells.