• Title/Summary/Keyword: IRF-3

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The Gut Microbiota of Pregnant Rats Alleviates Fetal Growth Restriction by Inhibiting the TLR9/MyD88 Pathway

  • Hui Tang;Hanmei Li;Dan Li;Jing Peng;Xian Zhang;Weitao Yang
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1213-1227
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    • 2023
  • Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8+ T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

  • Dong Hyun Kim;Hee Young Kim;Won-Woo Lee
    • IMMUNE NETWORK
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    • v.21 no.5
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    • pp.33.1-33.19
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    • 2021
  • IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8+ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8+ T cells and features of IL-1R+ CD8+ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8+ T cells. Further, IL-1β enhances the effector function of CD8+ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8+ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8+ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8+ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

Identification of Tumor Suppressor Loci on the Long Arm of Chromosome 5 in Primary Small Cell Lung Cancers (원발성 소세포폐암에서 염색체 5번의 장완에 위치한 종양억제유전자좌의 확인)

  • Cho, Eun-Song;Kim, Ho-Guen;Cho, Chul-Ho;Chang, Joon;Chung, Kyung-Young;Kim, Young-Sam;Park, Jae-Min;Kim, Sung-Kyu;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.1
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    • pp.49-59
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    • 2000
  • Backgrounds : Recent cytogenetic studies indicated that long of the long arm of chromosome 5 is a frequent event in small cell lung canær (SCLC), suggesting the presence of a tumor suppressor gene in its place. To map the precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 15 primary SCLCs. Methods : The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Nineteen polymorphic microsatellite markers located in the long arm of chromosome 5 were used in the microsatellite analysis. Results : We found that ten (66.7%) of 15 tumors exhibited LOH in at least one of tested microsatellite markers. Two (13%) of 10 tumors exhibiting LOH lost a larger area in chromosome 5q. LOH was observed in five common deleted regions at 5q. Among those areas, LOH between 5q34-qter and 5q35.2-35.3 was most frequent (75%). LOH was also observed in more than 50% of the tumors at four other regions, between 5q14-15 and 5q23-31, 5q31.1, 5q31.3-33.3, and 5q34-35. Three of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 2.5% (7 of 285) of the loci tested. Conclusion : Our data demonstrated that at least five tumor-suppressor loci exist in the long arm of chromosome 5 and that they may play an important role in small cell lung cancer tumorigenesis.

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An Analysis of Change in Beginner Science Teacher's Classroom Interaction through Mentoring Program (멘토링을 통한 초임중등과학교사의 수업에서의 교사.학생 상호작용 변화 분석)

  • Nam, Jeong-Hee;Lee, Sun-Duck;Lim, Jai-Hang;Moon, Seong-Bae
    • Journal of The Korean Association For Science Education
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    • v.30 no.8
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    • pp.953-970
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    • 2010
  • The purpose of this study was to investigate the change of teacher-student interaction in a beginner secondary science teachers' class through collaborative mentoring program. Three experienced science teachers as mentors and three beginner science teachers as mentees were participated in this study. Mentors have been teaching science secondary school for more than 13 years with specialty in science education, and mentees have been teaching less than three years in secondary schools. They were matched one-toone on grounded characteristics that were revealed from pre-interview. Data collection consisted of lesson plans of mentees' classes, videotaped lessons of mentees, consultation meetings between mentors and mentees, and interviews with mentees as well as mentors. The consultation meetings and interviews were audiotaped and then transcribed with the videotaped lessons. To examine the change in teacher-student interactions, the lesson observed after four sessions of mentoring was compared to the lesson before mentoring on the basis of the analytical framework that was developed based on the interpretative approach. The analytical framework addresses the four aspects of teacher-student interaction, which include beginner of interaction (initiation), the types of the question, the student response and the feedback. After four sessions of collaborative mentoring, the beginner science teacher's classroom interactions were initiated by students more often. Teachers' questions increasingly turned into thought-provoking queries that required higherorder thinking. The students responded in the form of statements instead of asking question more frequently. Also, teachers provided more delayed feedback than immediate feedback. These changes of interaction patterns showed that students took a leading role in classroom interaction and they were encouraged to think. From this result, we argue that the beginner science teachers developed the ability to make students think and to support them in coming to an understanding of knowledge through a collaborative mentoring program.