Skip Navigation LinksHome > October 2012 - Volume 60 - Issue 7 > Long-Acting Beta 2 Agonists Suppress IP-10 Expression in Hum...
Journal of Investigative Medicine:
doi: 10.231/JIM.0b013e3182673ff9
Original Articles

Long-Acting Beta 2 Agonists Suppress IP-10 Expression in Human Bronchial Epithelial Cells

Chien, Jien-Wen MD*; Chu, Yu-Te MD†‡; Yang, San-Nan MD,PhD†§; Kuo, Chang-Hung MD†∥; Wang, Wei-Li MD; Kuo, Po-Lin PhD¶**; Jong, Yuh-Jyh MD,PhD†§∥; Hung, Chih-Hsing MD, PhD†§∥††‡‡

Collapse Box


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.

Conclusion: 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.

Copyright © 2012 by the American Federation for Medical Research.


Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.