(S,S)-formoterol increases the production of IL-4 in mast cells and the airways of a murine asthma model

Daniel Abraha, Seong H. Cho, Devendra K. Agrawal, Jae M. Park, Chad K. Oh

Research output: Contribution to journalArticle

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Abstract

Background: Racemic formoterol is an equimolar mixture of (R,R)- and (S,S)-formoterol. Several studies have shown (S,S)-formoterol to have proinflammatory effects. We previously reported that (S)-albuterol increased the secretion of histamine and interleukin (IL)-4 in murine mast cells. We thus hypothesized that (S,S)-formoterol promotes asthma by enhancing IL-4 production in mast cells of the asthmatic airway. Methods: Murine and human mast cells were stimulated by high affinity IgE receptor (FcεRI) cross-linking or with phorbol myristate acetate/calcium ionophore A23187 (PMA/A23187). Jurkat T cells were stimulated with PMA. Cells were pretreated with either (R,R)- or (S,S)-formoterol. Ovalbumin (OVA)-sensitized BALB/c mice were pretreated with (R,R)- or (S,S)-formoterol before each intranasal OVA challenge for 10 days. Bronchoalveolar lavage fluid was obtained from the mice. The levels of IL-4, histamine and PGD2 were measured. Early and late allergic responses (EAR and LAR, respectively) to OVA challenge and airway hyperresponsiveness (AHR) were measured. Results: (S,S)-formoterol enhanced the production of IL-4, histamine, and PGD2 in mast cells, whereas (R,R)-formoterol had no effect. Neither (S,S)- nor (R,R)-formoterol had effect on IL-4 production in Jurkat T cells. In OVA-challenged mice, (S,S)-formoterol increased IL-4 secretion, whereas (R,R)-formoterol had no effect. Finally, (S,S)-formoterol enhanced the inflammatory changes in the peribronchial and perivascular areas without affecting EAR, LAR or AHR, whereas (R,R)-formoterol reduced EAR, LAR and AHR as well as cellular infiltration in the lung tissue of these mice. Conclusion: (S,S)-formoterol may exert adverse effects in asthma control by activating mast cells to produce proinflammatory mediators such as IL-4.

Original languageEnglish
Pages (from-to)380-388
Number of pages9
JournalInternational Archives of Allergy and Immunology
Volume133
Issue number4
DOIs
StatePublished - 2004

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Mast Cells
Interleukin-4
Asthma
Ovalbumin
Histamine
Prostaglandin D2
Jurkat Cells
Formoterol Fumarate
T-Lymphocytes
IgE Receptors
Calcium Ionophores
Albuterol
Calcimycin
Bronchoalveolar Lavage Fluid
Tetradecanoylphorbol Acetate

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

(S,S)-formoterol increases the production of IL-4 in mast cells and the airways of a murine asthma model. / Abraha, Daniel; Cho, Seong H.; Agrawal, Devendra K.; Park, Jae M.; Oh, Chad K.

In: International Archives of Allergy and Immunology, Vol. 133, No. 4, 2004, p. 380-388.

Research output: Contribution to journalArticle

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title = "(S,S)-formoterol increases the production of IL-4 in mast cells and the airways of a murine asthma model",
abstract = "Background: Racemic formoterol is an equimolar mixture of (R,R)- and (S,S)-formoterol. Several studies have shown (S,S)-formoterol to have proinflammatory effects. We previously reported that (S)-albuterol increased the secretion of histamine and interleukin (IL)-4 in murine mast cells. We thus hypothesized that (S,S)-formoterol promotes asthma by enhancing IL-4 production in mast cells of the asthmatic airway. Methods: Murine and human mast cells were stimulated by high affinity IgE receptor (FcεRI) cross-linking or with phorbol myristate acetate/calcium ionophore A23187 (PMA/A23187). Jurkat T cells were stimulated with PMA. Cells were pretreated with either (R,R)- or (S,S)-formoterol. Ovalbumin (OVA)-sensitized BALB/c mice were pretreated with (R,R)- or (S,S)-formoterol before each intranasal OVA challenge for 10 days. Bronchoalveolar lavage fluid was obtained from the mice. The levels of IL-4, histamine and PGD2 were measured. Early and late allergic responses (EAR and LAR, respectively) to OVA challenge and airway hyperresponsiveness (AHR) were measured. Results: (S,S)-formoterol enhanced the production of IL-4, histamine, and PGD2 in mast cells, whereas (R,R)-formoterol had no effect. Neither (S,S)- nor (R,R)-formoterol had effect on IL-4 production in Jurkat T cells. In OVA-challenged mice, (S,S)-formoterol increased IL-4 secretion, whereas (R,R)-formoterol had no effect. Finally, (S,S)-formoterol enhanced the inflammatory changes in the peribronchial and perivascular areas without affecting EAR, LAR or AHR, whereas (R,R)-formoterol reduced EAR, LAR and AHR as well as cellular infiltration in the lung tissue of these mice. Conclusion: (S,S)-formoterol may exert adverse effects in asthma control by activating mast cells to produce proinflammatory mediators such as IL-4.",
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T1 - (S,S)-formoterol increases the production of IL-4 in mast cells and the airways of a murine asthma model

AU - Abraha, Daniel

AU - Cho, Seong H.

AU - Agrawal, Devendra K.

AU - Park, Jae M.

AU - Oh, Chad K.

PY - 2004

Y1 - 2004

N2 - Background: Racemic formoterol is an equimolar mixture of (R,R)- and (S,S)-formoterol. Several studies have shown (S,S)-formoterol to have proinflammatory effects. We previously reported that (S)-albuterol increased the secretion of histamine and interleukin (IL)-4 in murine mast cells. We thus hypothesized that (S,S)-formoterol promotes asthma by enhancing IL-4 production in mast cells of the asthmatic airway. Methods: Murine and human mast cells were stimulated by high affinity IgE receptor (FcεRI) cross-linking or with phorbol myristate acetate/calcium ionophore A23187 (PMA/A23187). Jurkat T cells were stimulated with PMA. Cells were pretreated with either (R,R)- or (S,S)-formoterol. Ovalbumin (OVA)-sensitized BALB/c mice were pretreated with (R,R)- or (S,S)-formoterol before each intranasal OVA challenge for 10 days. Bronchoalveolar lavage fluid was obtained from the mice. The levels of IL-4, histamine and PGD2 were measured. Early and late allergic responses (EAR and LAR, respectively) to OVA challenge and airway hyperresponsiveness (AHR) were measured. Results: (S,S)-formoterol enhanced the production of IL-4, histamine, and PGD2 in mast cells, whereas (R,R)-formoterol had no effect. Neither (S,S)- nor (R,R)-formoterol had effect on IL-4 production in Jurkat T cells. In OVA-challenged mice, (S,S)-formoterol increased IL-4 secretion, whereas (R,R)-formoterol had no effect. Finally, (S,S)-formoterol enhanced the inflammatory changes in the peribronchial and perivascular areas without affecting EAR, LAR or AHR, whereas (R,R)-formoterol reduced EAR, LAR and AHR as well as cellular infiltration in the lung tissue of these mice. Conclusion: (S,S)-formoterol may exert adverse effects in asthma control by activating mast cells to produce proinflammatory mediators such as IL-4.

AB - Background: Racemic formoterol is an equimolar mixture of (R,R)- and (S,S)-formoterol. Several studies have shown (S,S)-formoterol to have proinflammatory effects. We previously reported that (S)-albuterol increased the secretion of histamine and interleukin (IL)-4 in murine mast cells. We thus hypothesized that (S,S)-formoterol promotes asthma by enhancing IL-4 production in mast cells of the asthmatic airway. Methods: Murine and human mast cells were stimulated by high affinity IgE receptor (FcεRI) cross-linking or with phorbol myristate acetate/calcium ionophore A23187 (PMA/A23187). Jurkat T cells were stimulated with PMA. Cells were pretreated with either (R,R)- or (S,S)-formoterol. Ovalbumin (OVA)-sensitized BALB/c mice were pretreated with (R,R)- or (S,S)-formoterol before each intranasal OVA challenge for 10 days. Bronchoalveolar lavage fluid was obtained from the mice. The levels of IL-4, histamine and PGD2 were measured. Early and late allergic responses (EAR and LAR, respectively) to OVA challenge and airway hyperresponsiveness (AHR) were measured. Results: (S,S)-formoterol enhanced the production of IL-4, histamine, and PGD2 in mast cells, whereas (R,R)-formoterol had no effect. Neither (S,S)- nor (R,R)-formoterol had effect on IL-4 production in Jurkat T cells. In OVA-challenged mice, (S,S)-formoterol increased IL-4 secretion, whereas (R,R)-formoterol had no effect. Finally, (S,S)-formoterol enhanced the inflammatory changes in the peribronchial and perivascular areas without affecting EAR, LAR or AHR, whereas (R,R)-formoterol reduced EAR, LAR and AHR as well as cellular infiltration in the lung tissue of these mice. Conclusion: (S,S)-formoterol may exert adverse effects in asthma control by activating mast cells to produce proinflammatory mediators such as IL-4.

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U2 - 10.1159/000077358

DO - 10.1159/000077358

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VL - 133

SP - 380

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JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

SN - 1018-2438

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