RESUMO
Vascular endothelium is a semi-permeable barrier that regulates the flow of nutrients, ions, cytokines and immune cells between blood and tissues. Barrier properties of endothelium, its ability to regenerate and the potential for secretion of inflammatory mediators play a crucial role in maintaining local tissue homeostasis. The lung vascular endothelial cells were shown to be infected by human rhinovirus (HRV) and generate antiviral, inflammatory and cytopathic responses. The current study reveals that in the long-time manner, the lung vascular endothelium may efficiently limit the HRV replication via the IFN-dependent 2'-5'-oligoadenylate synthetase 1 activation. This leads to the restoration of integrity accompanied by the up-regulation of adherens and tight junctions, increase of metabolic activity and proliferation rate. Secondly, HRV16-infected cells show delayed and transient up-regulation of the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor, angiopoietin 1 and 2, and neuropilin-1, as well as VEGF receptors. The lung vascular endothelium infected with HRV may limit the infection, recover in time, and regain barrier properties and metabolic functions, thus leading to the restoration of integrated barrier tissue.
Assuntos
Rhinovirus , Fator A de Crescimento do Endotélio Vascular , 2',5'-Oligoadenilato Sintetase , Angiopoietina-1/metabolismo , Antivirais , Citocinas/metabolismo , Células Endoteliais , Endotélio Vascular , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interferons , Pulmão , Neuropilina-1/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Replicação ViralRESUMO
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-ß, 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-ß, 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.
Assuntos
Endotélio Vascular/imunologia , Infecções por Picornaviridae/imunologia , Rhinovirus/imunologia , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/imunologia , Endotélio Vascular/virologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Células Endoteliais da Veia Umbilical Humana/virologia , Humanos , Interferon beta/genética , Interferon beta/imunologia , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/virologia , Receptores Imunológicos , Rhinovirus/genética , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologiaRESUMO
Irritable bowel syndrome (IBS), with the prevalence of 10%-20 % of the population has become an emerging problem worldwide. IBS is a functional gastrointestinal (GI) disorder characterized by abdominal pain or discomfort and altered bowel habits. The etiology of IBS contains genetic, psychological, and immunological factors, and has not been fully elucidated; of note, recent studies also point at environmental pollution and its role in the development of functional GI diseases. In this review we focus on several environmental factors, such as bacterial contamination, air pollution, radiation and even stress as potential triggers of IBS. We discuss associated disturbances in homeostasis, such as changes in intestinal microbiome and related pathophysiological mechanisms. Based on the effect of environmental factors on the GI tract, we also propose novel targets in IBS treatment.
