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Lymphotoxin β receptor signaling induces IL-8 production in human bronchial epithelial cells.

Mikami Y, Matsuzaki H, Horie M, Noguchi S, Jo T, Narumoto O, Kohyama T, Takizawa H, Nagase T, Yamauchi Y - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

ABSTRACT
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.

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Gene expression analysis of primary lung epithelial cells.We analyzed gene expression of LTβR and HVEM in several types of primary cells using the ZENBU database, which analyzed CAGE (cap analysis gene expression) of 432 normal primary cells. The lung epithelial cells strongly expressed the LTβR gene (A), but not the HVEM gene (B).ZENBU database URL: http://fantom.gsc.riken.jp/zenbu/
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pone-0114791-g001: Gene expression analysis of primary lung epithelial cells.We analyzed gene expression of LTβR and HVEM in several types of primary cells using the ZENBU database, which analyzed CAGE (cap analysis gene expression) of 432 normal primary cells. The lung epithelial cells strongly expressed the LTβR gene (A), but not the HVEM gene (B).ZENBU database URL: http://fantom.gsc.riken.jp/zenbu/

Mentions: We first evaluated gene expression of LTβR and HVEM in various types of primary cells using the “ZENBU” database of CAGE (cap analysis gene expression) results for 432 normal primary cells [22]. The bronchial epithelial cells expressed the LTβR gene strongly, but the HVEM gene less so (Fig. 1). We also examined the receptors' expression on the bronchial epithelial cell surface by flow cytometry, and the results were the same as those for the “ZENBU” database (strong LTβR expression, weaker HEVM expression) (Fig. 2).


Lymphotoxin β receptor signaling induces IL-8 production in human bronchial epithelial cells.

Mikami Y, Matsuzaki H, Horie M, Noguchi S, Jo T, Narumoto O, Kohyama T, Takizawa H, Nagase T, Yamauchi Y - PLoS ONE (2014)

Gene expression analysis of primary lung epithelial cells.We analyzed gene expression of LTβR and HVEM in several types of primary cells using the ZENBU database, which analyzed CAGE (cap analysis gene expression) of 432 normal primary cells. The lung epithelial cells strongly expressed the LTβR gene (A), but not the HVEM gene (B).ZENBU database URL: http://fantom.gsc.riken.jp/zenbu/
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263477&req=5

pone-0114791-g001: Gene expression analysis of primary lung epithelial cells.We analyzed gene expression of LTβR and HVEM in several types of primary cells using the ZENBU database, which analyzed CAGE (cap analysis gene expression) of 432 normal primary cells. The lung epithelial cells strongly expressed the LTβR gene (A), but not the HVEM gene (B).ZENBU database URL: http://fantom.gsc.riken.jp/zenbu/
Mentions: We first evaluated gene expression of LTβR and HVEM in various types of primary cells using the “ZENBU” database of CAGE (cap analysis gene expression) results for 432 normal primary cells [22]. The bronchial epithelial cells expressed the LTβR gene strongly, but the HVEM gene less so (Fig. 1). We also examined the receptors' expression on the bronchial epithelial cell surface by flow cytometry, and the results were the same as those for the “ZENBU” database (strong LTβR expression, weaker HEVM expression) (Fig. 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus