Double-stranded RNA poly(I:C) enhances matrix metalloproteinase mRNA expression in human nasal polyp epithelial cells

2009 ◽  
Vol 129 (sup562) ◽  
pp. 105-109 ◽  
Author(s):  
Jiyun Wang ◽  
So Watanabe ◽  
Satoshi Matsukura ◽  
Harumi Suzaki
Keyword(s):  
Epithelial Cells ◽  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Nasal Polyp ◽  
Poly I:C ◽  
Double Stranded Rna

Immune responses of porcine airway epithelial cells to poly(I:C), a synthetic analogue of viral double-stranded RNA

2015 ◽  
Vol 95 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Xiu-qin Yang ◽  
Liang Wang ◽  
Hai-tao Li ◽  
Di Liu
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Digital Gene Expression ◽  
Enrichment Analysis ◽  
Airway Epithelial Cells ◽  
Poly I:C ◽  
Synthetic Analogue ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Double Stranded Rna

Yang, X.-q., Wang, L., Li, H.-t. and Liu, D. 2015. Immune responses of porcine airway epithelial cells to poly(I:C), a synthetic analogue of viral double-stranded RNA. Can. J. Anim. Sci. 95: 13–20. Swine respiratory disease (SRD) is one of the most economically important diseases affecting the pig industry. The main infectious agents that cause SRD are viruses, but the molecular pathogenesis of viral SRD has not been extensively studied. Here, using digital gene expression tag profiling, the global transcriptional responses to poly(I:C), a synthetic analogue of viral double-stranded RNA, was analyzed in porcine airway epithelial cells (PAECs). The profiling analysis revealed numerous differentially expressed genes (DEGs), including unknown sequences in the porcine nucleotide databases. Gene ontology enrichment analysis showed that DEGs were mainly enriched in response to stress (GO: 0006950), of which, defense response is one sub-process. Poly(I:C) challenge induced a general inflammation response as indicated by marked upregulation of a variety of pathogen recognition receptors, interferon-stimulated genes, proinflammatory cytokines, and chemokines, together with the significant downregulation of anti-inflammatory molecules. Furthermore, the antiapoptotic pathway was triggered, as demonstrated by the significant suppression of molecules involved in the induction of apoptosis, together with the significant stimulation of putative inhibitor of apoptosis. The results indicate that PAECs initiated defense against poly(I:C) challenge through the inflammation responses, whereas poly(I:C) can utilize antiapoptotic pathway to evade host defense.

scholarly journals Toll-Like Receptor Agonists Modulate Wound Regeneration in Airway Epithelial Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2456 ◽  
Author(s):  
Anna Lewandowska-Polak ◽  
Małgorzata Brauncajs ◽  
Marzanna Jarzębska ◽  
Małgorzata Pawełczyk ◽  
Marcin Kurowski ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Airway Epithelium ◽  
Wound Repair ◽  
Repair Process ◽  
Airway Epithelial Cells ◽  
Poly I:C ◽  
Toll Like Receptors ◽  
Vegf Mrna ◽  
Microbial Products

Background: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. Objective: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. Methods: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. Results: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-β and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-β, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-β mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.

scholarly journals Toll-Like Receptor-3 Ligation-Induced Indoleamine 2, 3-Dioxygenase Expression in Human Trophoblasts

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4984-4992 ◽  
Author(s):  
Bo Wang ◽  
Kaori Koga ◽  
Yutaka Osuga ◽  
Ingrid Cardenas ◽  
Gentaro Izumi ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Conditioned Media ◽  
Poly I:C ◽  
Type I ◽  
Toll Like Receptor ◽  
Human Trophoblast ◽  
Double Stranded Rna ◽  
Indoleamine 2 ◽  
Polycytidylic Acid

Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades an essential amino acid, tryptophan, and plays a role in inhibiting the proliferation of T cells and intracellular pathogens. Inhibiting IDO in mice leads to fetal rejection, suggesting its significance in establishing pregnancy. Toll-like receptor 3 (TLR-3) is a key component of the innate immune system that recognizes viral double-stranded RNA and triggers immune reactions by producing type I interferon. Using a human trophoblast cell culture system, we studied the effect of TLR-3 ligation on IDO expression and function by treating trophoblasts with polyinosinic-polycytidylic acid [poly(I:C)] (a synthetic double stranded RNA, which mimics viral RNA). Real-time PCR and Western blot analysis revealed that IDO mRNA and protein expression was significantly induced by poly(I:C). The activity of IDO was also increased by poly(I:C) given that the l-kynurenine concentrations were elevated in conditioned media. Conditioned media from poly(I:C)-treated trophoblasts were found to inhibit the proliferation of human T cells significantly. Poly(I:C) was also shown to induce interferon (IFN)-β mRNA expression in trophoblasts. Recombinant human IFN-β increased IDO mRNA expression in trophoblasts more rapidly than poly(I:C). Pretreating with neutralizing antibody against IFN-β significantly suppressed IDO induction by poly(I:C). Collectively we have demonstrated that ligation of TLR-3 by poly(I:C) induces IDO expression in human first-trimester trophoblasts via an IFN-β-dependent pathway. These findings suggest that upon viral infection, trophoblasts induce IDO and in turn contribute to antimicrobial activity and maintenance of fetomaternal tolerance.

scholarly journals Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Tomohiro Ogawa ◽  
Keiko Kan-o ◽  
Ayaka Shiota ◽  
Akitaka Fujita ◽  
Yumiko Ishii ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Programmed Cell Death ◽  
Bronchial Epithelial Cells ◽  
Human Metapneumovirus ◽  
Poly I:C ◽  
Type I ◽  
Bronchial Epithelial ◽  
Double Stranded Rna ◽  
Programmed Cell Death 1

Bronchial epithelial cells are front sentinels eliciting innate and adaptive immunity to respiratory viral pathogens. Recognition of viral double-stranded RNA induces antiviral interferon (IFN) responses in bronchial epithelial cells. Co-inhibitory molecules programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) were also induced on bronchial epithelial cells, which bind programmed cell death 1 on T cell and inhibit the function of virus-specific cytotoxic T lymphocyte. A previous study showed that antiviral type I IFN increased PD-L1 and PD-L2 expression in cultured melanoma cells. However, it remains unknown whether antiviral IFNs affect PD-L1 and PD-L2 expression in bronchial epithelial cells. In addition, we previously reported that inhibition of PI3Kδ signaling enhanced antiviral IFN responses in human primary bronchial epithelial cells (PBECs). Here we assessed the effect of exogenous IFNs or a selective PI3Kδ inhibitor IC87114 on PD-L1 and PD-L2 in PBECs stimulated with a synthetic double-stranded RNA poly I:C or human metapneumovirus. Treatment with IFNβ or IFNλ increased PD-L1 and PD-L2, and IFNβ or IFNλ treatment plus poly I:C further increased both expressions. Treatment with IC87114 or transfection with siRNA targeting PI3K p110δ enhanced poly I:C–induced gene and protein expression of PD-L2, whereas IC87114 suppressed poly I:C–induced PD-L1. IC87114 enhanced poly I:C–induced gene expression of IFNβ, IFNλ, and IFN-regulated genes via increased TBK1 and IRF3 phosphorylation. Transfection with siIRF3 counteracted the enhancement of poly I:C–induced PD-L2 by IC87114, whereas IC87114 suppressed poly I:C–induced PD-L1 regardless of transfection with siNC or siIRF3. Similar effects of IC87114 on PD-L1 and PD-L2 expression were observed in human metapneumovirus–infected PBECs. We showed for the first time that type I and type III IFNs induced the expression of PD-L1 and PD-L2 in PBECs. Our findings suggest that during viral infections, inhibition of PI3Kδ differentially regulates PD-L1 and PD-L2 expression in bronchial epithelial cells.

Effect of Acacia Honey on Transforming Growth Factor-Beta-1-Induced Myofibroblast Differentiation and Matrix Metalloproteinase-9 Production in Nasal Polyp Fibroblasts

2019 ◽  
Vol 33 (5) ◽  
pp. 483-489
Author(s):  
Seung-Heon Shin ◽  
Mi-Kyung Ye ◽  
Dong-Won Lee ◽  
Mi-Hyun Che
Keyword(s):  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Nasal Polyp ◽  
Transforming Growth Factor Beta ◽  
Protein Production ◽  
Transforming Growth Factor ◽  
Myofibroblast Differentiation ◽  
Acacia Honey ◽  
Metalloproteinase 9 ◽  
Tgf Β1

BackgroundAcacia honey is known to have antioxidant, immune-modulatory, and antiproliferative properties. Nasal fibroblasts participate in local immune responses that control the recruitment of inflammatory cells and the production of extracellular matrix.ObjectivesThe aim of this study was to determine the effect of acacia honey on myofibroblast differentiation and matrix metalloproteinase-9 (MMP-9) production in nasal polyp fibroblasts.MethodsPrimary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). Reverse transcription-polymerase chain reaction and Western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), tissue inhibitors of matrix metalloproteinase-1, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad ( pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase ( pAMPK) were then determined by Western blotting.ResultsTGF-β1 stimulation increased α-SMA and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Acacia honey effectively suppressed α-SMA and MMP-9 mRNA expression and protein production. It also prevented phosphorylation of Smad 2/3 and AMPK.ConclusionAcacia honey can inhibit TGF-β1-induced myofibroblast differentiation and MMP-9 production in nasal fibroblasts. These results suggest that acacia honey might be useful for inhibiting nasal polyp formation.

Diesel exhaust enhances virus- and poly(I:C)-induced Toll-like receptor 3 expression and signaling in respiratory epithelial cells

2006 ◽  
Vol 290 (6) ◽  
pp. L1154-L1163 ◽  
Author(s):  
Jonathan Ciencewicki ◽  
Luisa Brighton ◽  
Wei-Dong Wu ◽  
Michael Madden ◽  
Ilona Jaspers
Keyword(s):  
Epithelial Cells ◽  
Diesel Exhaust ◽  
Poly I:C ◽  
Dominant Negative Mutant ◽  
Mutant Form ◽  
Toll Like Receptor ◽  
Respiratory Epithelial Cells ◽  
Double Stranded Rna ◽  
And Function ◽  
Respiratory Epithelial

Prior exposure of respiratory epithelial cells to an aqueous-trapped solution of diesel exhaust (DEas) enhances the susceptibility to influenza infections. Here, we examined the effect of DEas on the Toll-like receptor 3 (TLR3) pathway, which is responsible for the recognition of and response to viruses and double-stranded RNA. Flow cytometric and confocal microscopy analyses showed that TLR3 is predominantly expressed in the cytoplasm of respiratory epithelial cells. To examine the effect of DE on TLR3 expression and function, differentiated human bronchial or nasal epithelial cells as well as A549 cells were exposed to DEas and then infected with influenza A or treated with polyriboinosinic acid-polyribocytidylic acid [poly(I:C)], a synthetic form of double-stranded RNA. Exposure to DEas before infection with influenza or stimulation with poly(I:C) significantly upregulated the expression of TLR3. Additionally, preexposure to DEas significantly increased the poly(I:C)-induced expression of IL-6. Overexpression of a dominant-negative mutant form of TNF receptor-associated factor 6 reversed the effects of DEas on poly(I:C)-induced IL-6 expression, suggesting that the response was TLR3 dependent. Similarly, preexposure to DEas significantly increased nuclear levels of interferon regulatory factor 3 and the expression of IFN-β in response to poly(I:C). Pretreatment with wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, was able to abate the effect of DEas on poly(I:C)-induced IFN-β expression. Together, these results indicate that exposure of respiratory epithelial cells to DEas could potentially alter the response to viral infections by increasing the expression and function of TLR3.

scholarly journals Expression of the OAS Gene Family Is Highly Modulated in Subjects Affected by Juvenile Dermatomyositis, Resembling an Immune Response to a dsRNA Virus Infection

2018 ◽  
Vol 19 (9) ◽  
pp. 2786 ◽  
Author(s):  
Giuseppe Musumeci ◽  
Paola Castrogiovanni ◽  
Ignazio Barbagallo ◽  
Daniele Tibullo ◽  
Cristina Sanfilippo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Viral Infection ◽  
Gene Family ◽  
Gene Network ◽  
Juvenile Dermatomyositis ◽  
Poly I:C ◽  
Family Network ◽  
Double Stranded Rna ◽  
Muscle Biopsies

Background: Juvenile dermatomyositis (JDM) is a systemic, autoimmune, interferon (IFN)-mediated inflammatory muscle disorder that affects children younger than 18 years of age. JDM primarily affects the skin and the skeletal muscles. Interestingly, the role of viral infections has been hypothesized. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes have been thoroughly characterized as components of the IFN-induced antiviral system, and they are connected to several innate immune-activated diseases. The main purpose of the paper is to define the potential interrelationship between the OAS gene family network and the molecular events that characterize JDM along with double-stranded RNA (dsRNA) molecular pathways. Methods: We analyzed three microarray datasets obtained from the NCBI in order to verify the expression levels of the OAS gene family network in muscle biopsies (MBx) of JDM patients compared to healthy controls. Furthermore, From GSE51392, we decided to select significant gene expression profiles of primary nasal and bronchial epithelial cells isolated from healthy subjects and treated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA), a molecular pattern associated with viral infection. Results: The analysis showed that all OAS genes were modulated in JDM muscle biopsies. Furthermore, 99% of OASs gene family networks were significantly upregulated. Of importance, 39.9% of modulated genes in JDM overlapped with those of primary epithelial cells treated with poly(I:C). Moreover, the microarray analysis showed that the double-stranded dsRNA virus gene network was highly expressed. In addition, we showed that the innate/adaptive immunity markers were significantly expressed in JDM muscles biopsies. and that their levels were positively correlated to OAS gene family expression. Conclusion: OAS gene expression is extremely modulated in JDM as well as in the dsRNA viral gene network. These data lead us to speculate on the potential involvement of a viral infection as a trigger moment for this systemic autoimmune disease. Further in vitro and translational studies are needed to verify this hypothesis in order to strategically plan treatment interventions.

Hop Water Extract Inhibits Double-stranded RNA-induced Thymic Stromal Lymphopoietin Release from Human Nasal Epithelial Cells

2012 ◽  
Vol 26 (6) ◽  
pp. 433-438 ◽  
Author(s):  
Jun Fuchimoto ◽  
Takashi Kojima ◽  
Naoyuki Kobayashi ◽  
Tsuyoshi Ohkuni ◽  
Noriko Ogasawara ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Epithelial Cells ◽  
Water Extract ◽  
Thymic Stromal Lymphopoietin ◽  
Poly I:C ◽  
Dependent Manner ◽  
Double Stranded Rna ◽  
Nasal Epithelial Cells ◽  
Polycytidylic Acid ◽  
Human Nasal Epithelial Cells

Background Thymic stromal lymphopoietin (TSLP) acts as a master switch for allergic inflammation and plays a key role in allergic diseases, including allergic rhinitis. Double-stranded RNA (dsRNA) recognized by Toll-like receptor 3 (TLR3) strongly activates TSLP release from human human nasal epithelial cells (HNECs). Hop (Humulus lupulus L.) extracts have been shown to have potent pharmacologic effects on inflammation. Methods To investigate whether a hop water extract (HWE) prevents TSLP release from HNECs, human telomeras reverse transcriptase (hTERT)-transfected HNECs, used as a model of normal HNECs, were pretreated with HWE before treatment with the TLR3 ligand Polyinosine-polycytidylic acid (poly[I:C]). Results In the hTERT-transfected HNECs, treatment with HWE significantly reduced poly(I:C)-induced production and release of TSLP in a dose-dependent manner, as well as dexamethasone. Treatment with the protein kinase C (PKC) inhibitor GF109203X and NF-κB inhibitor IMD-0354 also reduced poly(I:C)-induced TSLP release from hTERT-transfected HNECs. Treatment with HWE efficiently prevented up-regulation of PKC activity by 12-O-tetradecanoyl phorbol-13-acetate but not NF-κB activity induced by IL-1β in hTERT-transfected HNECs. Conclusion Our results clearly indicated that HWE inhibited dsRNA-induced production and release of TSLP via a PKC signal pathway in HNECs and it may have potent preventive effects against allergic rhinitis.

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