scholarly journals HMSC-Derived Exosome Inhibited Th2 Cell Differentiation via Regulating miR-146a-5p/SERPINB2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jing Zhou ◽  
Yi Lu ◽  
Wei Wu ◽  
Yunhai Feng
Keyword(s):  
Target Genes ◽  
Specific Treatment ◽  
Allergic Inflammation ◽  
Underlying Mechanism ◽  
Human Mesenchymal Stem Cell ◽  
Th2 Cells ◽  
Luciferase Reporter ◽  
Antiallergic Activity ◽  
Th2 Cell ◽  
Blood Specimens

Background. Allergic rhinitis (AR) is a global disease without specific treatment. Human mesenchymal stem cell- (HMSC-) derived exosomes (HMSC-exos) have been implicated for the amelioration of allergic inflammation by delivering miR-146a-5p in a mouse asthma model. However, the antiallergic activity and the underlying mechanism of HMSC-exos in AR remain unclear. The present study aimed to investigate the role of HMSC-exos in the pathogenesis of AR. Materials and Methods. Blood specimens were collected from AR patients and healthy donators for investigation. HMSC and CD4+ T cells were used in the present study. Flow cytometry was used to characterize the population of Type 1 helper T (Th1) and Th2 cells. Specific siRNA and overexpressed plasmids were designed to silence or overexpress the expressions of miR-146a-5p and SERPINB2. Luciferase reporter assay was adopted to explore the binding site of miR-146a-5p and SERPINB2. Quantitative real-time PCR and immunoblots were performed to estimate the expression of target genes. Results. The population of Th2 cells was significantly elevated in AR patients as compared with that in healthy donators. HMSC-exos could decrease the expression of SERPINB2 and the differentiation of Th2 cells. miR-146a-5p in HMSC-exos exhibited consistent effects and lowered the expression of SERPINB2 by binding on its 3 ′ UTR region. Moreover, the differentiation of Th2 cells was promoted by SERPINB2 that could be reversed by HMSC-exos. Additionally, the miR-146a-5p expression was negatively associated with the SERPINB2 expression in the serum of AR patients. Conclusion. HMSC-exos could inhibit the differentiation of Th2 cells via the regulation of the miR-146a-5p/SERPINB2 pathway. miR-146a-5p and SERPINB2 could be applied as potential targets for AR treatment.

Hodgkin/Reed-Sternberg Cells Induce Fibroblasts to Secrete Eotaxin, a Potent Chemoattractant for T Cells and Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2065-2071 ◽  
Author(s):  
Franziska Jundt ◽  
Ioannis Anagnostopoulos ◽  
Kurt Bommert ◽  
Florian Emmerich ◽  
Gerd Müller ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Neutralizing Antibodies ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Allergic Inflammation ◽  
Dermal Fibroblasts ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Necrosis Factor

Hodgkin’s disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin’s disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin’s disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor- (TNF-) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF- by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin’s disease by contributing to eosinophil and T-lymphocyte recruitment.

scholarly journals MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

2017 ◽  
Vol 43 (5) ◽  
pp. 1974-1986 ◽  
Author(s):  
Ximing Wang ◽  
Yanxia Zhang ◽  
Hongshan Wang ◽  
Genshang Zhao ◽  
Xianen Fa
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
H9c2 Cells ◽  
Down Regulation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

scholarly journals IL-27 Suppresses Th2 Cell Development and Th2 Cytokines Production from Polarized Th2 Cells: A Novel Therapeutic Way for Th2-Mediated Allergic Inflammation

2007 ◽  
Vol 179 (7) ◽  
pp. 4415-4423 ◽  
Author(s):  
Tomohiro Yoshimoto ◽  
Takayuki Yoshimoto ◽  
Koubun Yasuda ◽  
Junichiro Mizuguchi ◽  
Kenji Nakanishi
Keyword(s):  
Allergic Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell ◽  
Novel Therapeutic

scholarly journals Mutations in FIGLA Associated With Premature Ovarian Insufficiency in a Chinese Population

2021 ◽  
Vol 8 ◽  
Author(s):  
Libin Mei ◽  
Yanru Huang ◽  
Xiaoling Wu ◽  
Huang He ◽  
Ronghui Ye ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Gene Mutations ◽  
Underlying Mechanism ◽  
Premature Ovarian Insufficiency ◽  
Hek293 Cells ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Wild Type ◽  
Ovarian Insufficiency

Objective: Premature ovarian insufficiency (POI) is one of the most common reproductive endocrinological causes of infertility in women of child-bearing age. The purpose of this study was to identify FIGLA gene mutations in Chinese patients with POI and to investigate the underlying mechanism.Methods: A total of 113 patients with idiopathic POI and 100 healthy controls were recruited for the analysis of FIGLA variants. Based on the identification of common mutations in the FIGLA, wild-type and mutant plasmids were constructed and transfected into HEK293 cells. Luciferase reporter genes were used to determine the effect of wild-type and mutant FIGLA genotypes on the transcriptional activity of its downstream targets, the zona pellucida glycoprotein genes ZP1, ZP2, and ZP3. Chromatin immunoprecipitation was used to determine the level of binding between wild-type and mutant FIGLA with the ZP1, ZP2, and ZP3 promoters.Results: Three different FIGLA mutations were identified in four patients with POI. Two patients carried the mutation c.11C>A (p.A4E), and the other two patients, respectively, carried the mutations c.625G>A (p.V209I) and c.84C>A (p.D28E). The luciferase reporter assay indicated that ZP1, ZP2, and ZP3 transcriptional activities were significantly reduced in individuals with FIGLA mutations. Chromatin immunoprecipitation indicated that the FIGLA mutation significantly decreased binding with the ZP1, ZP2, and ZP3 promoters.Conclusion:FIGLA mutation affects gene transcriptional regulation of its downstream target genes ZP1, ZP2, and ZP3, highlighting a new candidate genetic factor that causes POI. Our study demonstrates that FIGLA has a regulatory effect on reproduction-specific genes, thereby providing a basis for elucidating the specific regulatory mechanism of FIGLA in germ cell growth and development.

scholarly journals SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1443-1453 ◽  
Author(s):  
Helena Ahlfors ◽  
Amita Limaye ◽  
Laura L. Elo ◽  
Soile Tuomela ◽  
Mithila Burute ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Target Genes ◽  
Cell Polarization ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Th2 Cell ◽  
Th Cell ◽  
Gata3 Expression ◽  
Direct Binding

Abstract Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation.

scholarly journals Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Liang-qi Cao ◽  
Xue-wei Yang ◽  
Yu-bin Chen ◽  
Da-wei Zhang ◽  
Xiao-Feng Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Reporter Assays ◽  
Important Means ◽  
And Migration ◽  
Insight Into ◽  
Hcc Cells

Abstract Background As an important means of communication, exosomes play an important role in the development of hepatocellular carcinoma (HCC). Methods Bioinformatics analysis, dual-luciferase reporter assays, methylation-specific quantitative PCR, and ChIP-PCR analysis were used to gain insight into the underlying mechanism of miR-21 in HCC. Results The detection of miRNAs in exosomes of HCC showed that miR-21 expression in exosomes was positively correlated with the expression level of miR-21 in cells and negatively correlated with the expression of its target genes PTEN, PTENp1 and TETs. HCC cell-derived exosomes could increase miR-21 and p-Akt expression in HCC cells and downregulate the expression of PTEN, PTENp1 and TETs. MiR-21 inhibitors or PTENp1 overexpression vectors could weaken the effect of the abovementioned exosomes and simultaneously weaken their role in promoting cell proliferation and migration and inhibiting apoptosis. Further studies showed that miR-21 not only directly regulated the expression of PTEN, PTENp1 and TETs but also increased the methylation level of the PTENp1 promoter by regulating the expression of TETs, thereby inhibiting the expression of PTENp1 and further downregulating the expression of PTEN. Conclusions Exosomal miR-21 can regulate the expression of the tumor suppressor genes PTEN and PTENp1 in various ways and affect the growth of HCC cells.

scholarly journals Th2 cells and macrophages cooperatively induce allergic inflammation through histamine signaling

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248158
Author(s):  
Naruhito Iwasaki ◽  
Seigo Terawaki ◽  
Kouhei Shimizu ◽  
Daisuke Oikawa ◽  
Hirokazu Sakamoto ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Receptor Signaling ◽  
Alternatively Activated Macrophages ◽  
Th2 Cell ◽  
Histamine Production

Histamine, which is mainly produced by mast cells and basophils, participates in various allergic symptoms, and some studies have reported that macrophages also produce histamine. Moreover, recent studies have revealed that macrophages, especially alternatively activated macrophages (M2) induced by T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, participate in the pathogenesis of allergic diseases. The major source of Th2 cytokines is antigen-specific Th2 cells. To elucidate the relationship between histamine, macrophages, and Th2 cells in allergic inflammation, we established a macrophage-Th2 cell co-culture model in vitro and an antigen-specific Th2 cell transfer mouse model of rhinitis. In vitro analyses indicated that macrophages produce histamine by interacting with antigen-specific Th2 cells through the antigen. Furthermore, Th2 cells and macrophages cooperatively elicited rhinitis in the mouse model. We determined that histamine induces Th2- and macrophage-elicited sneezing responses through H1 receptor signaling, whereas it induces nasal eosinophil infiltrations through H4 receptor signaling. Collectively, these results indicate a novel histamine production mechanism by macrophages, in which Th2 cells and macrophages cooperatively induce nasal allergic inflammation through histamine signaling.

scholarly journals IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation.

2010 ◽  
Vol 184 (6) ◽  
pp. 3298-3298
Author(s):  
Tomohiro Yoshimoto ◽  
Takayuki Yoshimoto ◽  
Koubun Yasuda ◽  
Junichiro Mizuguchi ◽  
Kenji Nakanishi
Keyword(s):  
Allergic Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell ◽  
Novel Therapeutic

scholarly journals LncRNA DNM3OS promotes proliferation and inhibits apoptosis through modulating IGF1 expression by sponging MiR-126 in CHON-001 cells

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Di Ai ◽  
Fang Yu
Keyword(s):  
Cell Proliferation ◽  
Target Genes ◽  
Ectopic Expression ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Human Articular Cartilage ◽  
Related Factors ◽  
Mechanistic Investigation

Abstract Background As a degenerative disease, osteoarthritis (OA) greatly affects aged population. The human chondrocyte cell line CHON-001, derived from normal human articular cartilage, has been widely used in vitro in osteoarthritis models. In order to better understand the underlying mechanism of OA pathogenesis, this study was conducted to explore the effects of LncRNA dynamin 3 opposite strand (DNM3OS) on CHON-001 cells. Methods The expression levels of and correlation between DNM3OS and miR-126 that derived from OA and non-OA tissues were determined by quantitative real time (qRT)-PCR and Spearman’s correlation analysis. Cell viability, clone, migration, invasion and apoptosis were respectively determined by cell counting kit-8, colony formation, wound healing assay, transwell and flow cytometry. The target genes were predicted by starbase V2 and targetscan 7.2 and confirmed by luciferase reporter assay. The expressions of apoptosis-related factors were detected by Western blot. Results The expression of DNM3OS was down-regulated in OA patients. Functional assays demonstrated that ectopic expression of DNM3OS promoted the proliferation and inhibited apoptosis of CHON-001 cells, and that knocking down DNM3OS suppressed cell proliferation and induced apoptosis. Mechanistic investigation revealed that DNM3OS physically bound to the promoter of miR-126 and suppressed miR-126 expression. Decreased expression of DNM3OS was negatively correlated with miR-126 in OA patients. Furthermore, the effects of siDNM3OS on inhibiting cell proliferation and promoting apoptosis were partially reversed by miR-126 inhibitor. Meanwhile, type insulin-like growth factor-1 (IGF1) was identified as a target gene for miR-126 and was negatively associated with the miR-126 expression. Overexpressed IGF1 restored the effects of miR-126 mimic in suppressing cell proliferation and promoting apoptosis. Conclusion Our results showed that DNM3OS could affect the CHON-001 cell proliferation and apoptosis by regulating IGF1 by sponging miR-126.

Hodgkin/Reed-Sternberg Cells Induce Fibroblasts to Secrete Eotaxin, a Potent Chemoattractant for T Cells and Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2065-2071 ◽  
Author(s):  
Franziska Jundt ◽  
Ioannis Anagnostopoulos ◽  
Kurt Bommert ◽  
Florian Emmerich ◽  
Gerd Müller ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Neutralizing Antibodies ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Allergic Inflammation ◽  
Dermal Fibroblasts ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Necrosis Factor

Abstract Hodgkin’s disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin’s disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin’s disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor- (TNF-) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF- by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin’s disease by contributing to eosinophil and T-lymphocyte recruitment.

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