• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제46권1호
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• pp.3-11
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• 2020

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

• BMB Reports
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• 제50권1호
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• pp.25-30
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• 2017

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the $NF-{\kappa}B$ signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/$NF-{\kappa}B$ in astrocytes.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.641-647
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• 2017

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

• Parasites, Hosts and Diseases
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• 제47권2호
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• pp.117-124
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• 2009

Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by $IFN-{\gamma}$. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by $IFN-{\gamma}$. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by $IFN-{\gamma}$ in infected cells.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.235-240
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• 2010

Toll-like receptors (TLRs) functionally expressed in salivary epithelial cells, but their roles remain elusive. Among TLRs family, TLR3 is activated by dsRNA, a byproduct of viral infection. The aim of this study was to investigate the role of TLR3 in the inflammatory immune responses using HSG cells. Reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and ELISA were performed to identify expression of TLRs and TLR3-mediated chemokine inductions. The chemotaxis assay of activated T lymphocytes was also performed. Treatment of HSG cells with polyinosinic: polycytidylic acid (poly(I:C)) significantly increased interferon-$\gamma$-inducible protein 10 (IP-10), interferoninducible T-cell $\alpha$ chemoattractant (I-TAC), and regulated on activation, normal T-cells expressed and secreted (RANTES) gene expressions in a concentration-dependent manner. Anti-TLR3 antibody blocked the increases of IP-10 and I-TAC genes. Poly(I:C)-induced increases of IP-10 and I-TAC were also confirmed at protein levels from cell lysates, but their release into extracellular medium was detected only in IP-10. We found that the culture media from HSG cells stimulated with poly(I:C) significantly increases T lymphocyte migration. Our results suggest that TLR3 plays an important role in chemokine induction, particularly IP-10, in salivary epithelial cells.

• The Plant Pathology Journal
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• 제31권4호
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• pp.379-387
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• 2015

Melon necrotic spot virus (MNSV) was recently identified on watermelon (Citrullus vulgaris) in Korea, displaying as large necrotic spots and vein necrosis on the leaves and stems. The average occurrence of MNSV on watermelon was found to be 30-65% in Hapcheon and Andong City, respectively. Four isolates of the virus (MNSV-HW, MNSV-AW, MNSV-YW, and MNSV-SW) obtained from watermelon plants in different areas were non-pathogenic on ten general indicator plants, including Chenopodium quinoa, while they infected systemically six varieties of Cucurbitaceae. The virus particles purified by 10-40% sucrose density gradient centrifugation had a typical ultraviolet spectrum, with a minimum at 245 nm and a maximum at 260 nm. The morphology of the virus was spherical with a diameter of 28-30 nm. Virus particles were observed scattered throughout the cytoplasm of watermelon cells, but no crystals were detected. An ELISA was conducted using antiserum against MNSV-HW; the optimum concentrations of IgG and conjugated IgG for the assay were $1{\mu}l/ml$ and a 1:8,000-1:10,000 dilutions, respectively. Antiserum against MNSV-HW could capture specifically both MNSV-MN from melon and MNSV-HW from watermelon by IC/RT-PCR, and they were effectively detected with the same specific primer to produce product of 1,172 bp. The dsRNA of MNSV-HW had the same profile (4.5, 1.8, and 1.6 kb) as that of MNSV-MN from melon. The nucleotide sequence of the coat protein of MNSV-HW gave a different phylogenetic tree, having 17.2% difference in nucleotide sequence compared with MNSV isolates from melon.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제14권2호
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• pp.148-154
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• 2011

목적: 저자들은 지역사회에서, 로타바이러스 장염에 걸린 소아들에서 질환의 중증도와 로타바이러스 VP7 유전형과 VP4 유전형의 분포에 대해 알아보고자 하였다. 방법: 2007년 12월부터 2008년 6월까지 로타바이러스 장염으로 병원에 입원한 156명의 소아들에서 대변 샘플을 수집하였다. 모든 환자들에 대한 질환 중증도는 Vesikari 점수를 이용하여 평가하였다. 로타바이러스 ds-RNA를 분리한 후, 역전사 중합효소 연쇄반응과 다중 중합효소 연쇄반응을 이용하여 cDNA를 합성하였다. 마지막으로 유전형을 확인하였다. 결과: 156명의 환자 샘플에서, VP7(G)는 147명(94.2%)에서 확인되었고 VP4(P)는 140명(89.7%)에서 확인되었다. G1 유전형(147명 중 116명; 78.9%)과 P[8] 유전형(140명 중 137명)이 각각 가장 많았다. VP7과 VP4 조합형은 138명에서 확인할 수 있었는데, G1P[8] 조합형이 111명(80.4)으로 가장 많았다. 다른 조합형들은 종류가 다양하였고 분포가 낮았다. 전체 조합형 중 9.4%가 새로운 로타바이러스 백신에 포함되지 않은 것이었다. 로타바이러스 장염의 질환 중중도는 $11.8{\pm}3.3$ ($mean{\pm}2SD$)였다. 전체 환자에서 경증 내지 중등도가 37.8%였고, 중증은 62.2%였다. 결론: 로타바이러스 유전자 조합형 중 가장 흔한 것은 G1P[8]이었다. 새로운 백신에 포함되지 않은 유전자 조합형은 9.4%였다. 로타바이러스 장염으로 입원한 소아들의 질환 중증도분포는 경증과 중등도보다 중증에서 높게 나타났다.

• 환경생물
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• 제29권1호
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• pp.52-60
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• 2011

식물과 그 식물의 근권미생물과의 협력관계는 이미 오래전부터 관심을 받아왔고 지구 기후변화에 따라 식물과 그 근권미생물의 생태 및 지구환경에 대한 적응성은 막대한 지장을 받을 것으로 생각되어 왔다. 따라서 지구온난화에 따라 식물뿌리에 서식하는 근권미생물인 토양미 생물의 우점종이 어떻게 변화하는지에 대해 규명하고자 본 실험을 실시하였다. 우선 한국 식물생태계의 대표종인 소나무 (A), 잣나무 (B), 상수리나무 (C), 오리나무 (D) 를 선발하여 각각 실온인 $27^{\circ}C$와 $29^{\circ}C$(실온$+2^{\circ}C$), $31^{\circ}C$(실온$+4^{\circ}C$), $33^{\circ}C$(실온$+6^{\circ}C$)에서 1년 이상 성장시킨 후 이들의 뿌리토양을 무균적으로 채취하여 미생물 screening법과 colony counting을 통하여 각각의 군에서 우점종을 선별한 뒤 16S rRNA 분석에 의해 이들 각각의 우점종을 동정하였다. 그 결과 소나무 $27^{\circ}C$에서는 Bacillus cereus와 Enterobacter sp. CCBAU 15492, 소나무 $29^{\circ}C$에서는 Bacillus sp. 210_64와 Enterobacter sp. CCBAU 15492, 소나무 $31^{\circ}C$에서는 Bacillus sp. 210_64와 Enterobacter ludwigii, 소나무 $33^{\circ}C$에서는 Bacillus sp. 210_64와 Enterobacter sp. CCBAU 15492, Bacillus marisflavistrain DS6이 검출되었고, 잣나무 $27^{\circ}C$에서는 Bacillus cereus Q1, Pseudomonas sp. PR1-3, Arthrobacter woluwensisstrain CBU05/5295, 잣나무 $29^{\circ}C$에서는 Bacillus sp. G3, Pseudomonas sp. PR1-3, Bacillus sp. 210_24, 잣나무 $31^{\circ}C$에서는 Bacillus cereus Q1, Pseudomonas sp. PR1-3, 잣나무 $33^{\circ}C$에서는 Bacillus coagulans strain, Pseudomo-Dominant-species Change of Soil Microbes 59 nas sp. PR1-3, Chryseobacterium sp. COLI2, 상수리나무 $27^{\circ}C$에서는 Bacillus cereus strain B1, Pseudomonas putida strain W30, Arthrobacter woluwensis strain CBU05/5295, 상수리나무 $29^{\circ}C$에서는 Bacillus cereus strain CICC10185, Pseudomonas putida strain W30, 상수리나무 $31^{\circ}C$에서는 Bacillus cereus strain CG-T2, Pseudomonas sp. W15Feb9B, 상수리나무 $33^{\circ}C$에서는 Bacillus sp. CCBAU 51490, Arthrobacter woluwensis strain CBU05/5295, 오리나무 $27^{\circ}C$에서는 Bacillus sp. B18, Pseudomonas sp. PD 16, Enterobacter sp. CCBAU 15492, 오리나무 $29^{\circ}C$에서는 Rhodococcus erythropolis PR4, 오리나무 $31^{\circ}C$에서는 Enterobacter cloacae, Pseudomonas sp. PD 16, 오리나무 $33^{\circ}C$에서는 Bacillus subtilis strain SYH15, Pseudomonas sp. PD16을 우점종으로 동정하였다. 이 중 소나무는 $33^{\circ}C$에서 Bacillus marisflavi strain DS6가 $27{\sim}31^{\circ}C$에서는 발견되지 않다가 온도가 상승함에 따라 출현한 새로운 우점종으로 나타났고 잣나무에서는 $27^{\circ}C$에서 Bacillus cereus Q1, $29^{\circ}C$에서는 Bacillus sp. G3, $31^{\circ}C$에서는 Bacillus cereus Q1 등의 Bacillus속이 주요 우점종으로 나타났으나 온도가 가장 많이 상승한 $33^{\circ}C$에서는 Chryseobacterium sp. COLI2으로 우점종이 변한 것을 확인하였다. 본 실험은 차후 더 다양한 온도에서의 토양미생물 우점종 변화에 대한 연구가 진행되어야 할 것으로 사료되며 이들 연구결과들이 연계되어 지구온난화와 미생물의 관계, 그리고 새롭게 출현한 토양미생물과 식물간의 관계를 규명하는데 도움이 되는 데이터가 도출 될 것으로 기대된다.

• 한국식품영양과학회지
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• 제43권4호
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• pp.477-484
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• 2014

본 연구에서는 일반생강과 법제생강의 대장염 염증에 대한 억제 효과와 법제의 가공 처리가 일반생강의 염증 억제 효과보다 우수한 지를 비교하였다. Balb/c 수컷 마우스에 2.5% DSS로 궤양성 대장염을 유도하고, 일반생강과 법제생강 추출물 500 mg/kg을 투여하여 대장염의 염증 억제 효과를 연구하였다. 일반생강과 법제생강은 70% 에탄올로 열수 추출 및 농축하여 실험에 사용하였다. 일반생강과 법제생강 추출물 투여군 모두 대장 길이의 축소와 체중 감소가 대조군보다 유의적으로 억제되었다(P<0.05). 일반생강과 법제생강 추출물 투여군의 대장 길이는 7.6 cm와 8.0 cm로 법제생강 추출물 투여군의 대장 길이가 일반생강 추출물 투여군보다 더 길었다. 대장의 조직학적 관찰에서 대장의 길이의 축소 정도가 증가함에 따라 대장조직 점막층의 선와부의 파괴도 증가되었다. 대장염 염증 초기에 증가하는 염증성 biomarker인 혈청에서의 IFN-${\gamma}$, IL-6, TNF-${\alpha}$ 및 IL-12의 농도는 일반생강 추출물 투여군보다 법제생강 추출물 투여군에서 유의적으로 더 감소하였고, 대장 조직에서의 이들 사이토카인의 유전자 발현도 같은 경향을 나타내었다(P<0.05). 대장염 조직에서의 염증성 인자인 iNOS, COX-2의 유전자 발현에서도 일반생강군보다 법제생강군의 유전자 발현이 더 유의적으로 감소되었다. 이상의 결과로 DSS로 대장염이 유도된 마우스에서 일반생강과 법제생강의 추출물은 항 염증성 효과를 나타내었고, 법제생강 추출물의 대장염 염증 억제 효과가 일반생강 추출물보다 더 우수하였으며, 이는 법제가공 처리에 의해서 일반생강의 대장염 염증 억제효과가 증가되었다고 사료된다.