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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

The effect of Formoterol on the DC adoptive transfer model. BMDCs were stimulated with 10 μg/ml HDM in the presence or absence of 100 pM FORM for 24 hours. BMDCs were collected and washed twice with PBS, then 1.0 × 106 BMDCs in 50 μl PBS were administered to naïve BALC/c mice intranasally. Control mice were administrated 1.0 × 106 BMDCs without HDM and FORM stimulation (n = 6 in each group). On day 10, mice were challenged with 25 μg HDM. Twenty four hours later, mice were euthanized and BAL fluid and bronchial lymph nodes (LNs) were collected. (a) Total and differential cell counts in BAL fluids. After harvesting, bronchial lymph node cells were cultured in the presence of PMA and ionomycin. Concentrations of (b) IL-4, (c) IL-13, (d) IL-5 and (e) IL-17 in the supernatant were measured by ELISA. *p < 0.01, **p < 0.05.
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Fig6: The effect of Formoterol on the DC adoptive transfer model. BMDCs were stimulated with 10 μg/ml HDM in the presence or absence of 100 pM FORM for 24 hours. BMDCs were collected and washed twice with PBS, then 1.0 × 106 BMDCs in 50 μl PBS were administered to naïve BALC/c mice intranasally. Control mice were administrated 1.0 × 106 BMDCs without HDM and FORM stimulation (n = 6 in each group). On day 10, mice were challenged with 25 μg HDM. Twenty four hours later, mice were euthanized and BAL fluid and bronchial lymph nodes (LNs) were collected. (a) Total and differential cell counts in BAL fluids. After harvesting, bronchial lymph node cells were cultured in the presence of PMA and ionomycin. Concentrations of (b) IL-4, (c) IL-13, (d) IL-5 and (e) IL-17 in the supernatant were measured by ELISA. *p < 0.01, **p < 0.05.

Mentions: To examine whether the effect of FORM on HDM-induced airway inflammation in vivo depends on DCs, we performed adoptive transfer of HDM-pulsed BMDCs to naïve mice. When intranasal administration of HDM-pulsed DCs was followed by HDM challenge, the total number of cells (31.2 ± 13.5 × 104/ml), eosinophils (2.3 ± 1.4 × 104/ml) and neutrophils (13.1 ± 6.9 × 104/ml) in BAL fluids was significantly increased compared with mice given sham-pulsed DC and HDM challenge (Figure 6a). BAL cell counts in the latter group were total cells; 12.1 ± 6.3 × 104/ml, eosinophils; 0.4 ± 0.4 × 104/ml, and neutrophils; 3.6 ± 3.4 × 104/ml. When DCs pulsed with HDM in the presence of 100 pM FORM in vitro were administered to mice, the BAL cell numbers were significantly decreased in comparison to HDM group; total cells; 19.0 ± 3.3 × 104/ml (p < 0.05), eosinophils; 0.3 ± 0.3 × 104/ml (p < 0.05), and neutrophils; 5.0 ± 0.9 × 104/ml (p < 0.05), respectively (Figure 6a).Figure 6


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)

The effect of Formoterol on the DC adoptive transfer model. BMDCs were stimulated with 10 μg/ml HDM in the presence or absence of 100 pM FORM for 24 hours. BMDCs were collected and washed twice with PBS, then 1.0 × 106 BMDCs in 50 μl PBS were administered to naïve BALC/c mice intranasally. Control mice were administrated 1.0 × 106 BMDCs without HDM and FORM stimulation (n = 6 in each group). On day 10, mice were challenged with 25 μg HDM. Twenty four hours later, mice were euthanized and BAL fluid and bronchial lymph nodes (LNs) were collected. (a) Total and differential cell counts in BAL fluids. After harvesting, bronchial lymph node cells were cultured in the presence of PMA and ionomycin. Concentrations of (b) IL-4, (c) IL-13, (d) IL-5 and (e) IL-17 in the supernatant were measured by ELISA. *p < 0.01, **p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: The effect of Formoterol on the DC adoptive transfer model. BMDCs were stimulated with 10 μg/ml HDM in the presence or absence of 100 pM FORM for 24 hours. BMDCs were collected and washed twice with PBS, then 1.0 × 106 BMDCs in 50 μl PBS were administered to naïve BALC/c mice intranasally. Control mice were administrated 1.0 × 106 BMDCs without HDM and FORM stimulation (n = 6 in each group). On day 10, mice were challenged with 25 μg HDM. Twenty four hours later, mice were euthanized and BAL fluid and bronchial lymph nodes (LNs) were collected. (a) Total and differential cell counts in BAL fluids. After harvesting, bronchial lymph node cells were cultured in the presence of PMA and ionomycin. Concentrations of (b) IL-4, (c) IL-13, (d) IL-5 and (e) IL-17 in the supernatant were measured by ELISA. *p < 0.01, **p < 0.05.
Mentions: To examine whether the effect of FORM on HDM-induced airway inflammation in vivo depends on DCs, we performed adoptive transfer of HDM-pulsed BMDCs to naïve mice. When intranasal administration of HDM-pulsed DCs was followed by HDM challenge, the total number of cells (31.2 ± 13.5 × 104/ml), eosinophils (2.3 ± 1.4 × 104/ml) and neutrophils (13.1 ± 6.9 × 104/ml) in BAL fluids was significantly increased compared with mice given sham-pulsed DC and HDM challenge (Figure 6a). BAL cell counts in the latter group were total cells; 12.1 ± 6.3 × 104/ml, eosinophils; 0.4 ± 0.4 × 104/ml, and neutrophils; 3.6 ± 3.4 × 104/ml. When DCs pulsed with HDM in the presence of 100 pM FORM in vitro were administered to mice, the BAL cell numbers were significantly decreased in comparison to HDM group; total cells; 19.0 ± 3.3 × 104/ml (p < 0.05), eosinophils; 0.3 ± 0.3 × 104/ml (p < 0.05), and neutrophils; 5.0 ± 0.9 × 104/ml (p < 0.05), respectively (Figure 6a).Figure 6

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