Long-acting beta 2 agonists suppress IP-10 expression in human bronchial epithelial cells.
BACKGROUND
Interferon-γ-inducible protein (IP)-10 (CXCL10) is an important chemokine secreted by the airway epithelium that functions as a biomarker for virus-induced asthma. Long-acting beta 2 (β2) agonists (LABAs) are frequently used as inhaled medication for asthma and chronic obstructive pulmonary disease. However, previous research failed to investigate the effects of LABAs on IP-10 in bronchial epithelial cells.


OBJECTIVE
To study the effects and signaling pathways of formoterol and salmeterol on polyriboinosinic polyribocytidylic acid (poly I:C)-induced IP-10 expression in BEAS-2B cells.


METHODS
BEAS-2B cells were pretreated with formoterol and salmeterol for 2 hours before poly I:C stimulation. ICI 118551 (β2 adrenoreceptor antagonist) or mitogen-activated protein kinase (MAPK) inhibitors were added 30 minutes before LABAs were added. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to measure IP-10 protein and messenger RNA levels. Mitogen-activated protein kinase inhibitors and Western blotting were used to identify MAPK pathways, whereas bioassay revealed the MAPK functions.


RESULTS
Long-acting β2 agonists significantly down-regulated the poly I:C-induced IP-10 protein and messenger RNA expression in BEAS-2B cells. ICI 118551 reversed this effect. Forskolin, a cyclic adenosine monophosphate activator, produced a similar inhibitory effect. Western blotting showed that formoterol suppressed poly I:C-induced IP-10 expression via the c-Jun N-terminal kinase-c-Jun pathway.


CONCLUSIONS
Long-acting β2 agonists down-regulate poly I:C-induced IP-10 expression in BEAS-2B cells via the β2 adrenoreceptor-cyclic adenosine monophosphate and c-Jun N-terminal kinase/c-Jun pathways. Long-acting β2 agonists also inhibit IP-10 production in bronchial epithelial cells and may prolong viral elimination.
Department of Pediatrics, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan, ROC.
Jien-Wen
JW
Chien
Yu-Te
YT
Chu
San-Nan
SN
Yang
Chang-Hung
CH
Kuo
Wei-Li
WL
Wang
Po-Lin
PL
Kuo
Yuh-Jyh
YJ
Jong
Chih-Hsing
CH
Hung
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D000068299:Salmeterol Xinafoate
D058666:Adrenergic beta-2 Receptor Agonists; D004983:Ethanolamines; C104577:IP10-Mig receptor; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D018121:Receptors, Cytokine; D000068299:Salmeterol Xinafoate; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D011070:Poly I-C; D000420:Albuterol; D000068759:Formoterol Fumarate