development-an-vitro-assay-to-evaluate-contractile-function

Development of an <em>In Vitro</em> Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition

Fibrosis is often involved in the pathogenesis of various chronic progressive diseases such as interstitial pulmonary disease. Pathological hallmark is ...

The University of Tokyo Hospital

Asthma-related mortality has been decreasing due to inhaled corticosteroid use, but severe asthma remains a major clinical problem. One characteristic of severe asthma is resistance to steroid therapy, which is related to neutrophilic inflammation. Recently, the tumor necrosis factor superfamily member (TNFSF) 14/LIGHT has been recognized as a key mediator in severe asthmatic airway inflammation. However, the profiles and intracellular mechanisms of cytokine/chemokine production induced in cells by LIGHT are poorly understood. We aimed to elucidate the molecular mechanism of LIGHT-induced cytokine/chemokine production by bronchial epithelial cells. Human bronchial epithelial cells express lymphotoxin β receptor (LTβR), but not herpesvirus entry mediator, which are receptors for LIGHT. LIGHT induced various cytokines/chemokines, such as interleukin (IL)-6, oncostatin M, monocyte chemotactic protein-1, growth-regulated protein α and IL-8. Specific siRNA for LTβR attenuated IL-6 and IL-8 production by BEAS-2B and normal human bronchial epithelial cells. LIGHT activated intracellular signaling, such as mitogen-activated protein kinase and nuclear factor-κB (NF-κB) signaling. LIGHT also induced luciferase activity of NF-κB response element, but not of activator protein-1 or serum response element. Specific inhibitors of phosphorylation of extracellular signal-regulated kinase (Erk) and that of inhibitor κB attenuated IL-8 production, suggesting that LIGHT-LTβR signaling induces IL-8 production via the Erk and NF-κB pathways. LIGHT, via LTβR signaling, may contribute to exacerbation of airway neutrophilic inflammation through cytokine and chemokine production by bronchial epithelial cells.

Lymphotoxin β Receptor Signaling Induces IL-8 Production in Human Bronchial Epithelial Cells.

Lung metastasis showing radiographic findings of air-space consolidation is considered to be rare. This report describes the case of a man with progressive left lower lobe air-space consolidation with a history of hepatocellular carcinoma. The pulmonary lesion was initially suspected to be infection and later clinically diagnosed as primary adenocarcinoma of the lung. Although the patient was treated with systemic chemotherapy, the disease progressed very rapidly. A postmortem examination revealed that the alveolar spaces were filled with neoplastic cells subsequently proven to be metastases of combined hepatocellular and cholangiocarcinoma.

Pulmonary Metastasis of Combined Hepatocellular and Cholangiocarcinoma: A Unique Radiographic Presentation with Air-space Consolidation Masquerading as Pneumonia and Primary Pulmonary Adenocarcinoma.

Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are common respiratory disorders worldwide. Exacerbations of these diseases are frequent and worsen patients' respiratory condition and overall health. However, the mechanisms of exacerbation have not been fully elucidated. Recently, it was reported that interleukin (IL)-17A might play an important role in neutrophilic inflammation, which is characteristic of such exacerbations, through increased production of neutrophil chemoattractants. Therefore, we hypothesized that IL-17A was involved in the pathogenesis of acute exacerbation, due to viral infection in chronic inflammatory airway diseases. In this study, we assessed chemokine production by bronchial epithelial cells and investigated the underlying mechanisms. Comprehensive chemokine analysis showed that, compared with poly(I:C) alone, co-stimulation of BEAS-2B cells with IL-17A and poly(I:C) strongly induced production of such neutrophil chemoattractants as CXC chemokine ligand (CXCL)8, growth-related oncogene (GRO), and CXCL1. Co-stimulation synergistically induced CXCL8 and CXCL1 mRNA and protein production by BEAS-2B cells and normal human bronchial epithelial cells. Poly(I:C) induced chemokine expression by BEAS-2B cells mainly via Toll-like receptor 3/TIR-domain-containing adapter-inducing interferon-β-mediated signals. The co-stimulation with IL-17A and poly(I:C) markedly activated the p38 and extracellular-signal-regulated kinase 1/2 pathway, compared with poly(I:C), although there was little change in nuclear factor-κB translocation into the nucleus or the transcriptional activities of nuclear factor-κB and activator protein 1. IL-17A promoted stabilization of CXCL8 mRNA in BEAS-2B cells treated with poly(I:C). In conclusion, IL-17A appears to be involved in the pathogenesis of chronic inflammatory airway disease exacerbation, due to viral infection by promoting release of neutrophil chemoattractants from bronchial epithelial cells.

Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C) Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells.

Infections are an important cause of morbidity and mortality in patients with rheumatoid arthritis. Patients receiving immunosuppressive or anti-tumor necrosis factor (TNF) agents are vulnerable to fungal infections, including those derived from Aspergillus species. Detection of the Aspergillus galactomannan antigen in serum is useful for the early diagnosis of invasive aspergillosis in patients with hematological malignancies. However, its usefulness for detecting early invasive aspergillosis in rheumatoid arthritis patients remains unestablished.

Article	Year
Lymphotoxin β Receptor Signaling Induces IL-8 Production in Human Bronchial Epithelial Cells. PloS one\| PubMed ID: 25501580	2014
Pulmonary Metastasis of Combined Hepatocellular and Cholangiocarcinoma: A Unique Radiographic Presentation with Air-space Consolidation Masquerading as Pneumonia and Primary Pulmonary Adenoc... Internal medicine (Tokyo, Japan)\| PubMed ID: 26027993	2015
Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C) Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells. PloS one\| PubMed ID: 26505478	2015
Nonspecific elevation of serum Aspergillus galactomannan antigen levels in patients with rheumatoid arthritis. Respiratory investigation\| PubMed ID: 26718144	2016

Hirotaka Matsuzaki

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