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.

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.

OMC-2010 추출물이 마우스의 비장세포 cytokine 생성에 미치는 영향

배기상 ( Gi Sang Bae ),박경철 ( Kyoung Chel Park ),최선복 ( Sun Bok Choi ),조일주 ( Il Joo Jo ),서상완 ( Sang Wan Seo ),김종진 ( Jong Jin Kim ),신용국 ( Yong Kook Shin ),김민선 ( Min Sun Kim ),박규환 ( Kyu Hwan Park ),김현식 ( Hyu 대한본초학회 2012 大韓本草學會誌 Vol.27 No.5

Objective : This study was performed to estimate the effects of OMC-2010 extract on cytokine production in mouse spleen cells. Methods : Mouse spleen cells were pre-treated with ethanol and water extract of OMC-2010 for 1 h, then stimulated with lipopolysaccharide (LPS, 1 μg/ml) for 48 h. Then the cells were harvested for real-time reverse transcription polymerase chain reaction to detect cytokines. Results : OMC-2010 ethanol extract significantly inhibited the LPS-induced interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-5 mRNA expressions, but not shown such changes in IL-6, IL-4, IL-13. OMC-2010 water extract significantly inhibited the LPS-induced TNF-alpha, and IL-5 mRNA expressions, but not shown such changes in IL-1beta, IL-6, IL-4, IL-13. Conclusions : Theses results could suggest that both ethanol and water OMC-2010 extract could inhibit the TNF-alpha and IL-5 mRNA expression.

A genome-wide by PM₁₀ interaction study identifies novel loci for lung function near <i>BICD1</i> and <i>IL1RN-IL1F10</i> genes in Korean adults

Kim, Hyun-Jin,Seo, Yong-Seok,Sung, Joohon,Chae, Jeesoo,Yun, Jae Moon,Kwon, Hyuktae,Cho, Belong,Kim, Jong-Il,Park, Jin-Ho Elsevier 2020 CHEMOSPHERE - Vol.245 No.-

<P><B>Abstract</B></P> <P>Although several genome-wide interaction studies (GWIS) have been performed in specific European populations to understand the missing link between genetic and environmental factors for lung function, GWIS of Asian samples remain rare. Therefore, we performed a GWIS of exposure to air pollution to identify loci for lung function in Korean adult men. A total of 1826 adult men recruited from two health check-up centers were included in the analysis and the annual mean concentrations of ambient particulate matter with an aerodynamic diameter ≤10 μm (PM<SUB>10</SUB>) were used. In case of forced vital capacity (FVC), one SNP (rs12312730) that passed our genome-wide threshold of <I>p</I>int < 1 × 10–5 was detected in the intronic region of the <I>BICD1</I> gene on chromosome 12. In addition, we found two variants (rs6743376 and rs17042888) located near the <I>IL1RN-IL1F10</I> gene that were involved in the inflammatory response and associated with decreased FVC via interaction with PM<SUB>10</SUB> exposure. A stratified association analysis according to these SNP genotypes showed that PM<SUB>10</SUB> concentrations in subjects with one or two of the risk alleles, compared with those with the non-risk allele, were significantly correlated with a reduction in FVC. This pattern was replicated in another 892 Korean adult samples. The current study reports the first GWIS discovery in an Asian population: the <I>BICD1</I> and <I>IL1RN-IL1F10</I> genes may contribute to the decrease in FVC levels by interacting with PM<SUB>10</SUB> exposure.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Significant interactions between <I>BICD1 or IL1RN-IL1F10</I> and PM<SUB>10</SUB> for FVC were found. </LI> <LI> The several SNPs in these genes were more susceptible to FVC decline by PM<SUB>10</SUB>. </LI> <LI> For FVC, these interaction effects were reproducible in another sample. </LI> </UL> </P>

Early Phase of UVB - induced GM - CSF Upregulation in Epithelial Cell Line is not Totally Dependent on IL - 1α

Park, Kyoung Chan,Kim, Kyu Han,Ahn, Jong Seong,Chung, Jin Ho,Youn, Jai Il,Whang, Ji Hwan,Youn, Sang Woong,Kim, Young Gull,Koh, Woo Seok,Jung, Hyun Chae 대한피부과학회 1997 Annals of Dermatology Vol.9 No.4

Backgrounds : It was demonstrated that ultraviolet(UV) B light induces the release of IL-la in cultured human epithelial cell line and augmentation of GM-CSF production by UVB is reported to be mediated by IL-1α in the murine keratinocyte cell line Pam 212. Objective : The purpose of this study was to evaluate the effects of UVB on kinetic profile of IL-1 and GM-CSF mRNA expression and to see whether synthesis of GM-CSF by UVB can be completely inhibited by blocking IL-1α mediated pathway. Method : We used a competitive RT-PCR for measuring cytokine gene expression in epithelial cell line after UV radiation. Results : The IL-1α mRNA increased as early as 1h after UV irradiation, and then decreased at 3h after the irradiation. Thereafter, the response of IL-1α mRNA was upregulated with a second peak at 6h after the UV irradiation. However, mRNA for GM-CSF increased at 1h after UV light exposure and anti-IL-1α antibodies could only partially inhibit UV-augmented GMCSF production. Conclusion : UVB induced GM-CSF production seemed to be mainly mediated by UVB induced IL-1α but these results suggest that UVB may also induce GM-CSF production through an IL-1α independent pathway.

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol.26 No.4

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

Adiponectin is a negative regulator of NK cell cytotoxicity.

Kim, Kun-Yong,Kim, Jae Kwang,Han, Seung Hyun,Lim, Jong-Seok,Kim, Keun Il,Cho, Dae Ho,Lee, Myeong-Sok,Lee, Jeong-Hyung,Yoon, Do-Young,Yoon, Suk Ran,Chung, Jin Woong,Choi, Inpyo,Kim, Eunjoon,Yang, Young American Association of Immunologists 2006 Journal of Immunology Vol.176 No.10

<P>NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-kappaB activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.</P>

폐 한방슬러지로 배양한 팽이버섯(Flammulina velutipes) 추출물의 면역세포 활성화 효과

Jong-Jin Kim(김종진),Sang-Won Lee(이상원),Kyung-Wuk Park(박경욱),Kwon-Il Seo(서권일),Sung-Tae Yee(이성태) 한국생명과학회 2012 생명과학회지 Vol.22 No.6

일반적인 버섯 배지(미강 10%), 폐 한방슬러지를 10% 첨가한 배지, 그리고 미강 10%와 폐 한방슬러지 10%를 혼합한 배지에서 재배한 팽이버섯의 면역기능 강화효과를 알아보기 위해 물 추출물과 에탄올 추출물로 분리하여 실험하였다. 그 중 폐 한방슬러지 10%를 첨가한 배지에서 재배한 팽이버섯의 에탄올 추출물을 첨가하였을 때, 비장세포의 증식을 크게 유도하였으며 또한 IL-6, TNF-α, IFN-γ 분비를 유도하였다. 그리고 B세포의 증식반응과 면역글로불린 생산도 증가하였으며, 대식세포주의 일산화질소 분비와 IL-6, TNF-α, GM-CSF 생산도 증가하였다. 또한 복수암 유발 종양세포를 이용한 항종양 효과를 측정 한 결과 대조군의 평균 21.1일보다 실험군은 24.5일로 16.1%의 수명 연장효과가 나타났다. 따라서 폐 한방슬러지를 이용하면 수입에 의존하고 있는 버섯 재배 배지 원료를 절약할 수 있으며 면역세포조절 기능을 강화시키는 기능성 버섯을 얻을 수 있다고 생각한다. The objective of the current study was to determine the effects of the extracts isolated from the fruit body of Flammulina velutipes cultivated with oriental herbal plants on mouse splenocytes, B cells, and macrophages in vitro. The ethanol extracts B (EEB) directly induced the proliferation of spleen cells in a dose-dependent manner and increased IL-6, TNF-α, and IFN-γ synthesis. The EEB also increased the proliferation of B cells in a dose-dependent manner. The production of immunoglobulin M, G1, G2a, G2b, and IgG3 in the presence of the EEB increased progressively in the culture supernatant. When the EEB were used in macrophage cell line (RAW264.7) stimulation, there was a marked induction of NO synthesis in a dose-dependent manner and an increased IL-6, TNF-α, and GM-CSF synthesis. Intraperitoneal injection with EBB showed life prolongation effect of 16.1% in mice previously inoculated with sarcoma-180, respectively. These results suggest that the capacity of the EEB isolated from the fruit body of Flammulina velutipes cultivated with oriental herbal plants seems to act as a potent immunomodulator causing augmentation of immune cell activity, and with the absence of notable side-effects, Flammulina velutipes EEB could be used as a biological response modifier having possible therapeutic effects against immunological disorders. This study also showed that functional components of Flammulina velutipes were possibly improved by incorporating oriental herbal plants in a growth medium.

Comparison of Cytokine and Nitric Oxide Induction in Murine Macrophages between Whole Cell and Enzymatically Digested Bifidobacterium sp. Obtained from Monogastric Animals

Kim, Dong-Woon,Cho, Sung-Back,Lee, Hyun-Jeong,Chung, Wan-Tae,Kim, Kyoung-Hoon,HwangBo, Jong,Nam, In-Sik,Cho, Yong-Il,Yang, Mhan-Pyo,Chung, Il-Byung The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.4

The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin $(IL)-1{\beta}$, IL-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$ were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of $(TNF)-{\alpha}$ in the macrophage model as compared with the whole cells. By way of contrast, $(TNF)-{\alpha}$ production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.

Tumor necrosis factor-α and interleukin-1β increases CTRP1 expression in adipose tissue

Kim, Kun-yong,Kim, Hwa Young,Kim, Jae Hyeong,Lee, Chul-Ho,Kim, Do-Hyung,Lee, Young Ho,Han, Seung Hyun,Lim, Jong-Seok,Cho, Dae Ho,Lee, Myeong-Sok,Yoon, Sukjoon,Kim, Keun Il,Yoon, Do-Young,Yang, Young Elsevier 2006 FEBS letters Vol.580 No.16

<P><B>Abstract</B></P><P>CTRP1, a member of the CTRP superfamily, consists of an N-terminal signal peptide sequence followed by a variable region, a collagen repeat domain, and a C-terminal globular domain. CTRP1 is expressed at high levels in adipose tissues of LPS-stimulated Sprague-Dawley rats. The LPS-induced increase in CTRP1 gene expression was found to be mediated by TNF-α and IL-1β. Also, a high level of expression of CTRP1 mRNA was observed in adipose tissues of Zucker diabetic fatty (<I>fa/fa</I>) rats, compared to Sprague-Dawley rats in the absence of LPS stimulation. These findings indicate that CTRP1 expression may be associated with a low-grade chronic inflammation status in adipose tissues.</P>