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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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Comprehensive analysis of LIGHT-induced cytokine and chemokine production.BEAS-2B cells were stimulated with LIGHT (100 ng/ml) for 24 h, followed by determination of the protein levels of cytokines and chemokines by densitometry using a cytokine array. (A) The left image shows the unstimulated samples, while the right image shows the samples at 24 h after stimulation with LIGHT. (B) This table shows array mapping. The red color indicates cytokines that were upregulated more than twofold compared to the unstimulated sample. LIGHT induced inflammatory cytokines, such as GRO, GRO-α, oncostatin M, MCP-1, IL-6 and IL-8. (C) We investigated whether BEAS-2B cells produced LIGHT. THP-1 cells, which were used as a positive control, produced LIGHT when stimulated with PMA 50 ng/ml, but BEAS-2B cells did not.
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pone-0114791-g003: Comprehensive analysis of LIGHT-induced cytokine and chemokine production.BEAS-2B cells were stimulated with LIGHT (100 ng/ml) for 24 h, followed by determination of the protein levels of cytokines and chemokines by densitometry using a cytokine array. (A) The left image shows the unstimulated samples, while the right image shows the samples at 24 h after stimulation with LIGHT. (B) This table shows array mapping. The red color indicates cytokines that were upregulated more than twofold compared to the unstimulated sample. LIGHT induced inflammatory cytokines, such as GRO, GRO-α, oncostatin M, MCP-1, IL-6 and IL-8. (C) We investigated whether BEAS-2B cells produced LIGHT. THP-1 cells, which were used as a positive control, produced LIGHT when stimulated with PMA 50 ng/ml, but BEAS-2B cells did not.

Mentions: We used a cytokine array that detects 79 cytokines in order to analyze cytokines and chemokines secreted by bronchial epithelial cells (BEAS-2B) stimulated with LIGHT. As shown in Fig. 3B, LIGHT induced various cytokines, such as GRO, GRO-α, oncostatin M and MCP-1, and especially IL-6 and IL-8. These results indicate that LIGHT is a potent inducer of inflammatory cytokine and chemokine production by bronchial epithelial cells. We also demonstrated that BEAS-2B cells themselves did not produce LIGHT (Fig. 3C).


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)

Comprehensive analysis of LIGHT-induced cytokine and chemokine production.BEAS-2B cells were stimulated with LIGHT (100 ng/ml) for 24 h, followed by determination of the protein levels of cytokines and chemokines by densitometry using a cytokine array. (A) The left image shows the unstimulated samples, while the right image shows the samples at 24 h after stimulation with LIGHT. (B) This table shows array mapping. The red color indicates cytokines that were upregulated more than twofold compared to the unstimulated sample. LIGHT induced inflammatory cytokines, such as GRO, GRO-α, oncostatin M, MCP-1, IL-6 and IL-8. (C) We investigated whether BEAS-2B cells produced LIGHT. THP-1 cells, which were used as a positive control, produced LIGHT when stimulated with PMA 50 ng/ml, but BEAS-2B cells did not.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114791-g003: Comprehensive analysis of LIGHT-induced cytokine and chemokine production.BEAS-2B cells were stimulated with LIGHT (100 ng/ml) for 24 h, followed by determination of the protein levels of cytokines and chemokines by densitometry using a cytokine array. (A) The left image shows the unstimulated samples, while the right image shows the samples at 24 h after stimulation with LIGHT. (B) This table shows array mapping. The red color indicates cytokines that were upregulated more than twofold compared to the unstimulated sample. LIGHT induced inflammatory cytokines, such as GRO, GRO-α, oncostatin M, MCP-1, IL-6 and IL-8. (C) We investigated whether BEAS-2B cells produced LIGHT. THP-1 cells, which were used as a positive control, produced LIGHT when stimulated with PMA 50 ng/ml, but BEAS-2B cells did not.
Mentions: We used a cytokine array that detects 79 cytokines in order to analyze cytokines and chemokines secreted by bronchial epithelial cells (BEAS-2B) stimulated with LIGHT. As shown in Fig. 3B, LIGHT induced various cytokines, such as GRO, GRO-α, oncostatin M and MCP-1, and especially IL-6 and IL-8. These results indicate that LIGHT is a potent inducer of inflammatory cytokine and chemokine production by bronchial epithelial cells. We also demonstrated that BEAS-2B cells themselves did not produce LIGHT (Fig. 3C).

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