Sequential evolution of IL-17 responses in the early period of allograft rejection

Sang Il Min,하종원,박정규,Jae Kyung Won,Yang Jin Park,민승기,김상준 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.10

In addition to CD4+CD25+Foxp3+ regulatory T (Treg) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and Treg cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of Treg and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G+ cells were found to produce IL-17 during the early postoperative period and CD8+ as well as CD4+ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G+, CD4+, and even CD8+ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and Treg were found to gradually increase in both syngeneic and allogeneic recipients, Th17/Treg ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/Treg imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.

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.

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>

Comparison of Allergic Parameters between Whey Protein Concentrate and Its Hydrolysate in Rat Basophilic Leukemia (RBL)-2H3 Cells

Hana Kim,Sung-Il Ahn,Jin-Woo Jhoo,Gur-Yoo Kim 한국축산식품학회 2018 한국축산식품학회지 Vol.38 No.4

This study was conducted to compare the anti-allergic effects of a whey protein concentrate (WPC) and WPC hydrolysate. WPC hydrolysate was prepared using enzymatic digestion for 8 h with trypsin and α-chymotrypsin, after which it was freezedried. The allergic parameters assessed in rat basophilic leukemia (RBL)-2H3 cells were degranulation and release of β-hexosaminidase, release of tumor necrosis factor (TNF)-α, and changes in the expression of IL-1β, IL-4, and IL-10 by real time polymerase chain reaction (PCR). During preparation of the WPC hydrolysate, hydrolysis increased rapidly from 0 to 10 min and then gradually increased slowly from 1 h onwards, achieving a final degree of hydrolysis of 78.50%. The SDS-PAGE analysis revealed a reduction in the intensity of several protein bands in the WPC hydrolysate compared to the WPC. IgEinduced β-hexosaminidase release from RBL-2H3 cells was decreased to a higher degree following treatment with the hydrolysate compared to WPC treatment. W500 (500 μg/mL WPC) showed the least inhibition of β-hexosaminidase release, but there was no significant difference between W500 and W1000 (1,000 μg/mL) (p<0.05). H1000 (1,000 μg/mL WPC hydrolysate) inhibited β-hexosaminidase release by 39%. Compared to the control, treatment with H1000 decreased TNF-α secretion to 11.87 pg/mL. The gene expression levels of IL-1β, IL-4, and IL-13 were all significantly decreased in hydrolysate (p<0.05). In the case of IL-1β and IL-4, the expression levels in W1000 treated cells were decreased by 73.67% and 65%, respectively, and that of IL-13 was decreased by 66.43% compared to the control.

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>

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</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.

Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock.

Jung, In Duk,Lee, Min-Goo,Chang, Jeong Hyun,Lee, Jun Sik,Jeong, Young-Il,Lee, Chang-Min,Park, Won Sun,Han, Jin,Seo, Su-Kil,Lee, Sang Yong,Park, Yeong-Min Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.5

<P>Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO(-/-)) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO(-/-)- or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment.</P>

Differential Manifestation of Ocular Phenotypes in TALEN-mediated p19arf Knockout FVB/N and C57BL/6J mouse lines

Jin‑Sung Park,Joo‑Il Kim,Hyun‑Jin Lim,Soo‑Kyung Ryu,Euna Kwon,Kang‑Min Han,Ki‑Taek Nam,Han‑Woong Lee,Byeong‑Cheol Kang 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity. Object We carried out a study to investigate into the efect of genetic background on the manifestation of p19arf KO associated phenotypes. Methods We characterized the phenotypes of novel p19arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like efector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19arf-defcient mouse lines generated using homologous recombination. Results Ninety-fve percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19arf KO mouse. Conclusion Our fndings demonstrated surprisingly variable manifestation of p19arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.