Limits...
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.

Show MeSH

Related in: MedlinePlus

Expression of LTβR and HVEM receptors on BEAS-2B cells.BEAS-2B cells and THP-1 cells (positive control) were treated with anti-PE labeled LTβR antibody and anti-FITC labeled HVEM antibody. The fluorescence intensity was measured with a flow cytometer. THP-1 cells, a human monocytic cell line, were used as the positive control because they express both LTβR and HVEM on their cell surface. The fluorescence intensities of LTβR (A) and HVEM (B) suggest that BEAS-2B cells express LTβR but not HVEM.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263477&req=5

pone-0114791-g002: Expression of LTβR and HVEM receptors on BEAS-2B cells.BEAS-2B cells and THP-1 cells (positive control) were treated with anti-PE labeled LTβR antibody and anti-FITC labeled HVEM antibody. The fluorescence intensity was measured with a flow cytometer. THP-1 cells, a human monocytic cell line, were used as the positive control because they express both LTβR and HVEM on their cell surface. The fluorescence intensities of LTβR (A) and HVEM (B) suggest that BEAS-2B cells express LTβR but not HVEM.

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)

Expression of LTβR and HVEM receptors on BEAS-2B cells.BEAS-2B cells and THP-1 cells (positive control) were treated with anti-PE labeled LTβR antibody and anti-FITC labeled HVEM antibody. The fluorescence intensity was measured with a flow cytometer. THP-1 cells, a human monocytic cell line, were used as the positive control because they express both LTβR and HVEM on their cell surface. The fluorescence intensities of LTβR (A) and HVEM (B) suggest that BEAS-2B cells express LTβR but not HVEM.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114791-g002: Expression of LTβR and HVEM receptors on BEAS-2B cells.BEAS-2B cells and THP-1 cells (positive control) were treated with anti-PE labeled LTβR antibody and anti-FITC labeled HVEM antibody. The fluorescence intensity was measured with a flow cytometer. THP-1 cells, a human monocytic cell line, were used as the positive control because they express both LTβR and HVEM on their cell surface. The fluorescence intensities of LTβR (A) and HVEM (B) suggest that BEAS-2B cells express LTβR but not HVEM.
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