scholarly journals Up-regulated Vitamin D Receptor by Pelargonium Sidoides Extract EPs® 7630 Contributes to Rhinovirus Defence in Bronchial Epithelial Cells

2021 ◽  
Author(s):  
Michael Roth ◽  
Qingzhu Sun ◽  
Michael Tamm
Keyword(s):  
Vitamin D ◽  
Epithelial Cells ◽  
Vitamin D Receptor ◽  
Bronchial Epithelial Cells ◽  
Host Defence ◽  
Drug Preparation ◽  
Upper Respiratory Tract ◽  
Bronchial Epithelial ◽  
Pelargonium Sidoides ◽  
Tract Infections

Abstract Background: The Pelargonium sidoides herbal drug preparation EPs®7630 reduces the severity of viral upper respiratory tract infections. Vitamin D a secosteroid also improves anti-viral host defence. The anti-viral effect of both compounds was linked to similar signalling pathways in immune and epithelial cells. This study assessed if EPs®7630 modifies vitamin D receptor (VDR) expression by human bronchial epithelial cells. Methods: Bronchial epithelial cells were incubated with EPs®7630 over 48 hours before calcitriol stimulation and/or infection with Rhinovirus (RV)-16. The VDR expression and regulation was determined by Western-blotting. Intracellular signalling was studied by inhibition of mitogen activated protein kinases; Erk1/2, p38, and JNK. The anti-viral effect was assessed by immunofluorescence for RV-16 protein.Results: Treatment with EPs®7630 up-regulated the expression of the VDR through activation of Erk1/2 and thereby increased the cells sensitivity to calcitriol, reflected as the increased shift of the VDR from the cytosol into the nucleus. Compared to cells not pre-treated with EPs®7630 this VDR shift occurred at a 5.3 times lower calcitriol concentration. EPs®7630 increased Erk1/2 MAPK dependent signalling, but reduced the phosphorylation of p38. It had not effect on the activation and expression of JNK. EPs®7630 pre-treatment improved the anti-viral effect of vitamin D on RV-16 infection by 2.1 folds compared to vitamin D alone or to untreated cells. Furthermore, EPs®7630 improved the differentiation of epithelial cells by upregulating E-cadherin expression through Erk1/2.Conclusions: The results suggest that EPs®7630 increases host defence against rhinovirus infection by upregulating the VDR and thus increasing the response of epithelial cells to vitamin D.

scholarly journals Up-Regulated Vitamin D Receptor by Pelargonium sidoides Extract EPs® 7630 Contributes to Rhinovirus Defense in Bronchial Epithelial Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 172
Author(s):  
Michael Roth ◽  
Qingzhu Sun ◽  
Michael Tamm
Keyword(s):  
Vitamin D ◽  
Epithelial Cells ◽  
Host Defense ◽  
Vitamin D Receptor ◽  
Mapk Signaling ◽  
Bronchial Epithelial Cells ◽  
Upper Respiratory Tract ◽  
Bronchial Epithelial ◽  
Pelargonium Sidoides ◽  
Tract Infections

EPs®7630, extracted from Pelargonium sidoides, reduces the severity of viral upper respiratory tract infections. Vitamin D also improves anti-viral host defense through similar signaling pathways. This study assessed if EPs®7630 modifies vitamin D receptor (VDR) expression and function by human bronchial epithelial cells. Bronchial epithelial cells were incubated with EPs®7630 over 48 h before calcitriol stimulation and/or infection with Rhinovirus (RV)-16. Protein expression was determined by Western-blotting. Intracellular signaling of mitogen activated protein kinases (MAPK) was studied by chemical inhibitors. The anti-viral effect was assessed by immunofluorescence for RV-16 protein. EPs®7630 upregulated VDR expression through Erk1/2 MAPK and thereby increased the cell’s sensitivity to calcitriol. Compared ton untreated cells, the shift of the VDR into the nucleus at 5.3 times lower calcitriol concentration. EPs®7630 increased Erk1/2 MAPK signaling, but reduced p38 phosphorylation, and had no effect on Jun N-terminal kinase (JNK). EPs®7630 improved the anti-viral effect of vitamin D on RV-16 infection by 2.1 folds compared to vitamin D alone or to untreated cells. Furthermore, EPs®7630 improved the differentiation of epithelial cells by upregulating E-cadherin expression through Erk1/2. In conclusion, EPs®7630 increased host defense against Rhinovirus infection by upregulating the VDR and the differentiation of epithelial cells.

scholarly journals Interleukin 13 Exposure Enhances Vitamin D-Mediated Expression of the Human Cathelicidin Antimicrobial Peptide 18/LL-37 in Bronchial Epithelial Cells

2012 ◽  
Vol 80 (12) ◽  
pp. 4485-4494 ◽  
Author(s):  
J. A. Schrumpf ◽  
M. A. J. A. van Sterkenburg ◽  
R. M. Verhoosel ◽  
S. Zuyderduyn ◽  
P. S. Hiemstra
Keyword(s):  
Vitamin D ◽  
Epithelial Cells ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Vitamin D Receptor ◽  
Bronchial Epithelial Cells ◽  
Atopic Asthma ◽  
Interleukin 4 ◽  
Bronchial Epithelial ◽  
Vitamin D Levels

ABSTRACTVitamin D is an important regulator of the expression of antimicrobial peptides, and vitamin D deficiency is associated with respiratory infections. Regulating expression of antimicrobial peptides, such as the human cathelicidin antimicrobial peptide 18 (hCAP18)/LL-37, by vitamin D in bronchial epithelial cells requires local conversion of 25(OH)-vitamin D3(25D3) into its bioactive metabolite, 1,25(OH)2-vitamin D3(1,25D3), by CYP27B1. Low circulating vitamin D levels in childhood asthma are associated with more-severe exacerbations, which are often associated with infections. Atopic asthma is accompanied by Th2-driven inflammation mediated by cytokines such as interleukin 4 (IL-4) and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP18/LL-37 expression is unknown. Therefore, we investigated this with well-differentiated bronchial epithelial cells. To this end, cells were treated with IL-13 with and without 25D3, and expression of hCAP18/LL-37, CYP27B1, the 1,25D3-inactivating enzyme CYP24A1, and vitamin D receptor was assessed by quantitative PCR. We show that IL-13 enhances the ability of 25D3to increase expression of hCAP18/LL-37 and CYP24A1. In addition, exposure to IL-13 resulted in increased CYP27B1 expression, whereas vitamin D receptor (VDR) expression was not significantly affected. The enhancing effect of IL-13 on 25D3-mediated expression of hCAP18/LL-37 was further confirmed using SDS-PAGE Western blotting and immunofluorescence staining. In conclusion, we demonstrate that IL-13 induces vitamin D-dependent hCAP18/LL-37 expression, most likely by increasing CYP27B1. These data suggest that Th2 cytokines regulate the vitamin D metabolic pathway in bronchial epithelial cells.

scholarly journals Host Defence Peptide LL-37 Induces IL-6 Expression in Human Bronchial Epithelial Cells by Activation of the NF-κB Signaling Pathway

2008 ◽  
Vol 1 (3) ◽  
pp. 254-267 ◽  
Author(s):  
Jelena Pistolic ◽  
Celine Cosseau ◽  
Yuexin Li ◽  
Jie (Jessie) Yu ◽  
Niall C.J. Filewod ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Bronchial Epithelial Cells ◽  
Host Defence ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

scholarly journals Infection of bronchial epithelial cells by the human adenoviruses A12, B3 and C2 differently regulates the innate antiviral effector APOBEC3B

2021 ◽  
Author(s):  
Noémie Lejeune ◽  
Florian Poulain ◽  
Kévin Willemart ◽  
Zoé Blockx ◽  
Sarah Mathieu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Selection Pressure ◽  
Large Family ◽  
Bioinformatic Analysis ◽  
Bronchial Epithelial Cells ◽  
Transcriptional Level ◽  
Dna Viruses ◽  
Bronchial Epithelial ◽  
Human Adenoviruses ◽  
Tract Infections

Human adenoviruses (HAdVs) are a large family of DNA viruses counting more than 100 genotypes divided into seven species (A–G) and inducing respiratory tract infections, gastroenteritis and conjunctivitis. Genetically modified adenoviruses are also used as vaccines, gene therapies and anti-cancer treatments. The APOBEC3s are a family of cytidine deaminases that restrict viruses by introducing mutations in their genomes. Viruses developed different strategies to cope with the APOBEC3 selection pressure but nothing is known on the interplay between the APOBEC3s and the HAdVs. In this study, we focused on three HAdV strains: the B3 and C2 strains as they are very frequent and the A12 strain, less common but oncogenic in animal models. We demonstrated that the three HAdV strains induce a similar APOBEC3B upregulation at the transcriptional level. At the protein level however, the APOBEC3B is abundantly expressed during the HAdV-A12 and -C2 infection and shows a nuclear distribution. On the contrary, APOBEC3B is barely detectable in HAdV-B3-infected cells. APOBEC3B deaminase activity is detected in total protein extracts upon HAdV-A12 and -C2 infection. Bioinformatic analysis demonstrate that the HAdV-A12 genome bears a stronger APOBEC3 evolutionary footprint than the HAdV-C2 and HAdV-B3 genomes. Our results show that HAdV infection triggers the transcriptional upregulation of the antiviral innate effector APOBEC3B. The discrepancies between the APOBEC3B mRNA and protein levels might reflect the ability of some HAdV strains to antagonize the APOBEC3B protein. These findings point toward an involvement of APOBEC3B in HAdVs restriction and evolution. IMPORTANCE The APOBEC3 family of cytosine deaminases has important roles in antiviral innate immunity and cancer. Notably, APOBEC3A and/or APOBEC3B are actively upregulated by several DNA tumor viruses and contribute to transformation by introducing mutations in the cellular genome. Human adenoviruses (HAdVs) are a large family of DNA viruses causing generally asymptomatic infections in immunocompetent adults. HAdVs encode several oncogenes and some HAdV strains like HAdV-A12 induce tumors in hamsters and mice. Here, we show that HAdV infection specifically promotes the expression of the APOBEC3B gene. We report that infection with the A12 strain induces a strong expression of an enzymatically active APOBEC3B protein in bronchial epithelial cells. We provide bioinformatic evidences that HAdVs’ genomes and notably the A12 genome are under APOBEC3 selection pressure. Thus, APOBEC3B might contribute to adenoviral restriction, diversification and oncogenic potential of particular strains.

scholarly journals Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air–Liquid Interface Cultured Human Primary Bronchial Epithelial Cells

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1335
Author(s):  
Bram M. ter Ellen ◽  
Nilima Dinesh Kumar ◽  
Ellen M. Bouma ◽  
Berit Troost ◽  
Denise P.I. van de Pol ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Antiviral Activity ◽  
Bronchial Epithelial Cells ◽  
Liquid Interface ◽  
Post Inoculation ◽  
Upper Respiratory Tract ◽  
African Green Monkey Kidney ◽  
Bronchial Epithelial ◽  
Air Liquid Interface ◽  
Primary Bronchial Epithelial Cells

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro. First, we show that resveratrol and pterostilbene antiviral activity in African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly five rounds of replication, demonstrating the long-lasting effect of these compounds. Second, as the upper respiratory tract represents the initial site of SARS-CoV-2 replication, we also assessed antiviral activity in air–liquid interface (ALI) cultured human primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol and pterostilbene showed a strong antiviral effect in these cells up to 48 h post-infection. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to inhibit SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether these drugs are advantageous for COVID-19 treatment.

Cystic fibrosis bronchial epithelial cells have impaired ability to activate vitamin D

2016 ◽  
Vol 105 (7) ◽  
pp. 851-853 ◽  
Author(s):  
Terezia Pincikova ◽  
Emma Svedin ◽  
Erna Domsgen ◽  
Malin Flodström-Tullberg ◽  
Lena Hjelte
Keyword(s):  
Cystic Fibrosis ◽  
Vitamin D ◽  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Impaired Ability

scholarly journals Identification of Mannheimia haemolytica Adhesins Involved in Binding to Bovine Bronchial Epithelial Cells

2008 ◽  
Vol 77 (1) ◽  
pp. 446-455 ◽  
Author(s):  
Dagmara I. Kisiela ◽  
Charles J. Czuprynski
Keyword(s):  
Epithelial Cells ◽  
Protein A ◽  
Bacterial Pathogen ◽  
Protein Band ◽  
Bronchial Epithelial Cells ◽  
Surface Proteins ◽  
Mannheimia Haemolytica ◽  
Upper Respiratory Tract ◽  
Bronchial Epithelial

ABSTRACT Mannheimia haemolytica, a commensal organism of the upper respiratory tract in cattle, is the principal bacterial pathogen associated with the bovine respiratory disease complex. Adherence to the respiratory mucosa is a crucial event in its pathogenesis. However, the bacterial components that contribute to this process are not fully characterized. In this study, we demonstrated that M. haemolytica adhered to bovine bronchial epithelial cells (BBEC) in vitro and that adherence was inhibited by anti-M. haemolytica antibody. Western blot analysis of M. haemolytica proteins that bind to BBEC showed a dominant protein band with an apparent molecular mass of ∼30 kDa. Peptide sequences for the 30-kDa BBEC-binding proteins, as determined by liquid chromatography-tandem mass spectrometry, matched two M. haemolytica surface proteins: heat-modifiable outer membrane protein A (OmpA) and lipoprotein 1 (Lpp1). Western blotting showed that the 30-kDa protein band is recognized by both anti-M. haemolytica OmpA and anti-Lpp1 antibodies. Furthermore, incubation with anti-OmpA and anti-Lpp1 antibodies significantly inhibited M. haemolytica binding to BBEC monolayers. In summary, these results suggest that OmpA and Lpp1 contribute to adherence of M. haemolytica to bovine respiratory epithelial cells.

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