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Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC-L) was infected with HRV16. IFN-β, OAS-1, and PKR expression was assessed by real-time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN-β in the limitation of HRV16 replication, HMVEC-Ls were preincubated with anti-IFN-β Abs. To prove the involvement of OAS-1 and PKR in the IFNdependent limitation of HRV16 replication, HMVEC-Ls were transfected with respective siRNA. HRV16 stimulated IFN-β production and activated intracellular mechanisms of antiviral immunity based on OAS-1 and PKR activation. Blocking of IFN-β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS-1, PKR) and boosted replication of HRV16. Effective OAS-1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN-β-dependent intracellular mechanisms based on OAS-1 and PKR activity. [ABSTRACT FROM AUTHOR]

It is postulated that vaccination against tuberculosis with Bacillus Calmette-Gue'rin (BCG) vaccine may translate into lower incidence of respiratory tract infections by modulating the release of pro-inflammatory cytokines by innate immune cells. This modulation may be due to epigenetic changes in these cells resulting in an increase in the production of pro-inflammatory cytokines such as IL-1β, IL-6 or TNF-α. It is not known whether the pulmonary vascular endothelium equipped with molecular pattern recognition receptors (PRRs) and with entry receptors for human coronaviruses can be infected by them, or whether BCG vaccination may modulate its susceptibility to infection with these viruses. This study analyzes the effect of the HCoV 229E human coronavirus on human pulmonary vascular endothelium. Moreover, the influence of BCG sonicates on susceptibility to HCoV 229E endothelial infection and the generation of antiviral and inflammatory responses was assessed. [ABSTRACT FROM AUTHOR]

To the Editor, Human rhinovirus (HRV) belonging to the I Picornaviridae i family is a non-enveloped virus with a single-stranded, positive-sense RNA genome. (Figure S4) The effect of rhinovirus on the pulmonary vascular endothelium observed in our study is to a certain extent similar to its effect on the airway epithelium.1,2,4 GLO:1X5/01jun21:all14671-fig-0001.jpg PHOTO (COLOR): 1 Infection of human microvascular endothelial cells by human rhinovirus HRV16 and the influence on barrier properties. [Extracted from the article]

The effect of rhinovirus on airway epithelium is very well described. However, its influence on the vascular endothelium is unknown. The current study assesses the effect of rhinovirus HRV16 on the antiviral and inflammatory response in the human vascular endothelial cells (ECs). HRV16 increased IFN‐β, RANTES, and IP‐10 mRNA expression and protein release. HRV16 copy number in ECs reached maximal value 10 h after incubation. Increase in virus copies was accompanied by the enhancement of Toll‐ and RIG‐I‐like receptors: TLR3, RIG‐I, and MDA5. Additionally, HRV16 increased OAS‐1 and PKR mRNA expression, enzymes responsible for virus degradation and inhibition of replication. ICAM‐1 blockade decreased HRV16 copy number in ECs and inhibited IFN‐β, RANTES, IP‐10, OAS1, PKR, TLR3, RIG‐I, and MDA5 mRNA expression increase upon subsequent induction with HRV16. The vascular endothelium may be infected by human rhinovirus and generate antiviral and inflammatory innate response. Results of the study indicate the possible involvement of the vascular endothelium in the immunopathology of rhinoviral airway infections. [ABSTRACT FROM AUTHOR]

The use of novel research tools in microbial identification, including next generation sequencing, has enabled the analysis of complex relationships showing the potential importance of the gastrointestinal, skin and respiratory microbiome in the development of allergic inflammation and allergic diseases. The purpose of this work is to review the latest information on the effect of microbiota on the regulation of the immune response with particular emphasis on T2-dependent mechanisms in relation to the development of allergic diseases and asthma. [ABSTRACT FROM AUTHOR]

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL‐10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte‐derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7‐ketocholesterol (7‐kCH) – harmful oxidized form of cholesterol. The effect of E. coli LPS, 7‐kCH and ApoB100 on the barrier functions of HUVECs in real‐time cell electric impedance sensing system (RTCA‐DP) was assessed. Furthermore, the effect of 7‐kCH and ApoB100 on barrier functions of HUVECs co‐cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7‐kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL‐10 mRNA expression. In HUVECs co‐cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7‐kCH, IL‐10 mRNA expression was lower. E. coli LPS‐exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) may initiate autoimmunity as a result of molecular mimicry. The aim of this study was to compare the level of IgG antibodies to a specific epitope (P1 peptide) of human heat shock protein (Hsp)60 homologous to Hp Hsp60 (HspB) in the sera of healthy donors (HD), patients with Hp‐related gastritis or coronary heart disease (CHD), uninfected or with Hp infection confirmed by rapid urease test, histological examination (dyspeptic patients) the 13C urea breath test (13C UBT), and anti‐Hp antibodies (healthy donors, CHD patients). The Anti‐P1 IgG induction by Hp was verified by adsorption of sera with these bacteria and by experimental immunization of Caviae porcellus with Hp. Cytokine secretion by THP‐1Blue™ monocytes in response to P1 was also assessed. Anti‐P1 antibodies were detected in patients with gastritis or CHD infected with Hp and they were not found in uninfected individuals or asymptomatic carriers. No antibodies were raised against P2 in any group. Reduced cross‐reactivity to P1 was exhibited by sera adsorbed with Hp. Caviae porcellus infected with Hp produced anti‐P1 autoantibodies. THP‐1XBlue™ monocytes responded to P1 by production of proinflammatory cytokines. Autoantibodies against P1 in Hp‐positive patients with gastritis or CHD and upregulation of proinflammatory cytokines by P1 may contribute to the pathogenesis of Hp infection. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression of this disease remains unknown. Our laboratory has demonstrated that Bruton’s tyrosine kinase (Btk) is a critical regulator of pro-inflammatory processes in the lungs and that Btk controls expression of matrix metalloproteinase-9 (MMP-9) in the alveolar compartment. For this study apolipoprotein E null (ApoE—/ —) mice were exposed to SHS to facilitate study in a COPD/atherosclerosis comorbidity model. We applied two types of treatments, animals received either a pharmacological inhibitor of Btk orMMP-9 specific siRNA to minimizeMMP-9 expression in endothelial cells or neutrophils. We have shown that these treatments had a protective effect in the lung. We have noted a decrease in alveolar changes related to SHS induced inflammation in treated animals. In summary, we are presenting a novel concept in the field of COPD, i.e., that Btk may be a new drug target for this disease. Moreover, cell specific targeting ofMMP-9 may also benefit patients affected by this disease. [ABSTRACT FROM AUTHOR]

Wstęp: Wirusy układu oddechowego w tym rinowirusy (HRV) są najczęstszymi czynnikami wywołującymi infekcje dolnych i górnych dróg oddechowych. Rinowirusy są odpowiedzialne za co najmniej połowę wszystkich przypadków przeziębienia oraz są najczęstszą przyczyną ciężkich zaostrzeń astmy u dzieci i dorosłych (60-80%). Zakażenia rinowirusowe występują w środowisku od wczesnej wiosny do późnej jesieni. Dodatkowo, sezonowe szczyty dla HRV oraz innych wirusów oddechowych często się nakładają, co zwiększa ryzyko kilkukrotnych infekcji tym samym bądź innym wirusem oddechowym w sezonie. Obecnie nie ma badań wskazujących na to, jak długo mogą utrzymywać się wrodzone mechanizmy oporności na ponowną infekcję wirusami oddechowymi w komórkach śródbłonka naczyń płucnych. Nie zostało również wyjaśnione, przez jaki okres czasu infekcja rinowirusowa poprzez indukcję odpowiedzi zapalnej i przeciwwirusowej może zabezpieczać komórki przed ponowną infekcją tym samym lub innym wirusem oddechowym. Cel: Głównym celem pracy było badanie długości utrzymywania się wrodzonych mechanizmów oporności na ponowną infekcję rinowiusem HRV16 w komórkach śródbłonka naczyń płucnych. Materiały i Metody: Ludzkie komórki śródbłonka naczyniowego płuc (HMVEC-L) inkubowano z HRV16 (MOI3) przez 3h. Następnie w 72h wymieniano podłoże i dodawano do komórek świeże medium. W 5 dobie od pierwotnego zakażenia, komórki ponownie infekowano wirusem HRV16 (MOI3) przez 3h i hodowano dalej przez 5, 24 i 72 godziny. Aktywność odpowiedzi zapalnej (IL-6, IL-8, RANTES, IP-10) i przeciwwirusowwej (IFNβ, IFNλ, OAS1, PKR) oceniono za pomocą real-time PCR, testu ELISA oraz cytometrii przepływowej. Wyniki: HRV16 w krótkim czasie po infekcji zwiększał ekspresję interferonów, enzymów OAS1 i PKR odpowiedzialnych za wewnątrzkomórkowe mechanizmy zahamowania replikacji wirusowej oraz chemokin i cytokin zapalnych. Po ponownej ekspozycji na HRV16 nie zaobserwowano zwiększonej aktywności odpowiedzi zapalnej i przeciwwirusowej, natomiast zaobserwowano wzrost ekspresji mRNA i białka dla enzymów OAS1 i PKR w porównaniu do pierwotnej infekcji. Podsumowanie: Zainfekowane komórki śródbłonka naczyń płucnych wykazują długoterminową zwiększoną aktywność wewnątrzkomórkowych mechanizmów walki przeciwwirusowej, w wyniku których komórki te mogą nie być podatne na ponowne zakażeniem tym samym bądź innym wirusem oddechowym. [ABSTRACT FROM AUTHOR]

Bacteriophages show anti-inflammatory properties by affecting the immune system by lowering the level of cytokines and other pro-inflammatory mediators. The epithelium of the respiratory tract is an important mechanical defensive barrier of immunity. It also plays a key role in controlling many of the functions of the airways. It is a source of cytokines and mediators involved in the inflammatory process. In this study, a divergent, time- and concentration-dependent effect on the synthesis of 15-HETE as well as the regenerative properties of the respiratory epithelium was demonstrated. The results obtained in the study may allow for a better understanding of the influence of bacteriophages present in the human body on immunological processes. [ABSTRACT FROM AUTHOR]

Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC-L) was infected with HRV16. IFN-β, OAS-1, and PKR expression was assessed by real-time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN-β in the limitation of HRV16 replication, HMVEC-Ls were preincubated with anti-IFN-β Abs. To prove the involvement of OAS-1 and PKR in the IFN-dependent limitation of HRV16 replication, HMVEC-Ls were transfected with respective siRNA. HRV16 stimulated IFN-β production and activated intracellular mechanisms of antiviral immunity based on OAS-1 and PKR activation. Blocking of IFN-β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS-1, PKR) and boosted replication of HRV16. Effective OAS-1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN-β-dependent intracellular mechanisms based on OAS-1 and PKR activity., (© 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Aim: To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover., Methods: In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation., Results: We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway., Conclusion: In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier., Competing Interests: Conflict-of-interest statement: The authors have no competing interests.