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Published on: June 25, 2012
β2-Agonists inhibit TNF-α-induced ICAM-1 expression in human airway parasympathetic neurons
Zhenying Nie1, Allison D Fryer, David B Jacoby
1Division of Pulmonary and Critical Care Medicine, Medical School Oregon Health and Science University, Portland, Oregon, USA. niez@ohsu.edu
Background:
Major basic protein released from eosinophils to airway parasympathetic nerves blocks inhibitory M(2) muscarinic receptors on the parasympathetic nerves, increasing acetylcholine release and potentiating reflex bronchoconstriction. Recruitment of eosinophils to airway parasympathetic neurons requires neural expression of both intercellular adhesion molecular-1 (ICAM-1) and eotaxin. We have shown that inflammatory cytokines induce eotaxin and ICAM-1 expression in parasympathetic neurons.
Objective:
To test whether the β(2) agonist albuterol, which is used to treat asthma, changes TNF-alpha-induced eotaxin and ICAM-1 expression in human parasympathetic neurons.
Methods:
Parasympathetic neurons were isolated from human tracheas and grown in serum-free medium for one week. Cells were incubated with either (R)-albuterol (the active isomer), (S)-albuterol (the inactive isomer) or (R,S)-albuterol for 90 minutes before adding 2 ng/ml TNF-alpha for another 4 hours (for mRNA) or 24 hours (for protein).
Results And Conclusions:
Baseline expression of eotaxin and ICAM-1 were not changed by any isomer of albuterol as measured by real time RT-PCR. TNF-alpha induced ICAM-1 expression was significantly inhibited by (R)-albuterol in a dose dependent manner, but not by (S) or (R,S)-albuterol. Eotaxin expression was not changed by TNF-alpha or by any isomer of albuterol. The β-receptor antagonist propranolol blocked the inhibitory effect of (R)-albuterol on TNF-alpha-induced ICAM-1 expression.
Clinical Implication:
The suppressive effect of (R)-albuterol on neural ICAM-1 expression may be an additional mechanism for decreasing bronchoconstriction, since it would decrease eosinophil recruitment to the airway nerves.
Insights
The asthma medication albuterol, specifically its active (R)-isomer, can reduce airway inflammation by inhibiting ICAM-1 expression on nerve cells. This mechanism may help decrease bronchoconstriction by reducing eosinophil recruitment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Eosinophil release of major basic protein blocks inhibitory M(2) muscarinic receptors on airway parasympathetic nerves.
- This blockage increases acetylcholine release, potentiating reflex bronchoconstriction.
- Eosinophil recruitment to airway parasympathetic neurons requires neural expression of intercellular adhesion molecular-1 (ICAM-1) and eotaxin, which are induced by inflammatory cytokines.
Purpose of the Study:
- To investigate whether the beta(2) agonist albuterol affects TNF-alpha-induced eotaxin and ICAM-1 expression in human parasympathetic neurons.
- To determine if different isomers of albuterol have varying effects on these expressions.
Main Methods:
- Human parasympathetic neurons were isolated from tracheas and cultured.
- Cells were treated with (R)-albuterol, (S)-albuterol, or (R,S)-albuterol.
- Subsequently, cells were exposed to TNF-alpha to assess ICAM-1 and eotaxin expression via RT-PCR and protein analysis.
Main Results:
- Albuterol isomers did not alter baseline eotaxin or ICAM-1 expression.
- (R)-albuterol significantly inhibited TNF-alpha-induced ICAM-1 expression in a dose-dependent manner.
- Neither (S)-albuterol nor (R,S)-albuterol inhibited ICAM-1 expression, and eotaxin expression remained unchanged.
Conclusions:
- The active isomer of albuterol, (R)-albuterol, suppresses neural ICAM-1 expression induced by TNF-alpha.
- This suppression may represent an additional mechanism by which albuterol reduces bronchoconstriction by limiting eosinophil recruitment to airway nerves.
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