β2-Agonists inhibit TNF-α-induced ICAM-1 expression in human airway parasympathetic neurons.
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).


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.


CONCLUSIONS
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.
Division of Pulmonary and Critical Care Medicine, Medical School Oregon Health and Science University, Portland, Oregon, USA. niez@ohsu.edu
Zhenying
Z
Nie
Allison D
AD
Fryer
David B
DB
Jacoby
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D054413:Chemokine CCL11 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D011433:Propranolol / Q000494:pharmacology; D013237:Stereoisomerism; D014019:Tissue Donors; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D054413:Chemokine CCL11; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011433:Propranolol; D000420:Albuterol