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β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells.

Kato G, Takahashi K, Tashiro H, Kurata K, Shirai H, Kimura S, Hayashi S - BMC Immunol. (2014)

Bottom Line: The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro.These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM.Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. go.kato.go@gmail.com.

ABSTRACT

Background: Long-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs.

Results: We assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation.

Conclusion: These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

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Related in: MedlinePlus

Formoterol- and epinephrine-attenuated cytokine production from DCs in a β2adrenergic receptor and dose dependent manner. BMDCs, 1.0 × 106/ml in complete media, were stimulated by 10 μg HDM in the presence of various concentrations of FORM or epinephrine for 24 hours. Supernatants were collected, and concentrations of (a) IL-23, (b) IL-6 and (c) IL-10 were measured by ELISA. *p < 0.01, **p < 0.05.
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Fig4: Formoterol- and epinephrine-attenuated cytokine production from DCs in a β2adrenergic receptor and dose dependent manner. BMDCs, 1.0 × 106/ml in complete media, were stimulated by 10 μg HDM in the presence of various concentrations of FORM or epinephrine for 24 hours. Supernatants were collected, and concentrations of (a) IL-23, (b) IL-6 and (c) IL-10 were measured by ELISA. *p < 0.01, **p < 0.05.

Mentions: We hypothesized that the suppression of T cell responses by FORM in vivo was mediated by DCs. We therefore examined the effect of FORM on cytokine production by BMDCs in vitro. BMDCs produced IL-23 and IL-6 after HDM stimulation. IL-23 production was suppressed by both FORM and epinephrine in a dose dependent manner (Figure 4a), where the effect of FORM was 10,000 times stronger than epinephrine. IL-6 production was also suppressed by FORM, but not by epinephrine at concentrations of up to 10−7 M (Figure 4b). IL-10 production from DCs was enhanced by FORM and epinephrine in a dose dependent manner (Figure 4c).Figure 4


β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells.

Kato G, Takahashi K, Tashiro H, Kurata K, Shirai H, Kimura S, Hayashi S - BMC Immunol. (2014)

Formoterol- and epinephrine-attenuated cytokine production from DCs in a β2adrenergic receptor and dose dependent manner. BMDCs, 1.0 × 106/ml in complete media, were stimulated by 10 μg HDM in the presence of various concentrations of FORM or epinephrine for 24 hours. Supernatants were collected, and concentrations of (a) IL-23, (b) IL-6 and (c) IL-10 were measured by ELISA. *p < 0.01, **p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4228181&req=5

Fig4: Formoterol- and epinephrine-attenuated cytokine production from DCs in a β2adrenergic receptor and dose dependent manner. BMDCs, 1.0 × 106/ml in complete media, were stimulated by 10 μg HDM in the presence of various concentrations of FORM or epinephrine for 24 hours. Supernatants were collected, and concentrations of (a) IL-23, (b) IL-6 and (c) IL-10 were measured by ELISA. *p < 0.01, **p < 0.05.
Mentions: We hypothesized that the suppression of T cell responses by FORM in vivo was mediated by DCs. We therefore examined the effect of FORM on cytokine production by BMDCs in vitro. BMDCs produced IL-23 and IL-6 after HDM stimulation. IL-23 production was suppressed by both FORM and epinephrine in a dose dependent manner (Figure 4a), where the effect of FORM was 10,000 times stronger than epinephrine. IL-6 production was also suppressed by FORM, but not by epinephrine at concentrations of up to 10−7 M (Figure 4b). IL-10 production from DCs was enhanced by FORM and epinephrine in a dose dependent manner (Figure 4c).Figure 4

Bottom Line: The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro.These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM.Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. go.kato.go@gmail.com.

ABSTRACT

Background: Long-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs.

Results: We assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation.

Conclusion: These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

Show MeSH
Related in: MedlinePlus