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Long-Acting Beta 2 Agonists Suppress IP-10 Expression in Human Bronchial Epithelial Cells
  1. Jien-Wen Chien, MD*,
  2. Yu-Te Chu, MD†‡,
  3. San-Nan Yang, MD,PhD†§,
  4. Chang-Hung Kuo, MD†∥,
  5. Wei-Li Wang, MD,
  6. Po-Lin Kuo, PhD¶**,
  7. Yuh-Jyh Jong, MD,PhD†§∥,
  8. Chih-Hsing Hung, MD, PhD†§∥††‡‡
  1. From the *Department of Pediatrics, Changhua Christian Hospital, Changhua City, Changhua County; †Department of Pediatrics, Kaohsiung Medical University Hospital; ‡Department of Pediatrics, True Generation Hospital; §Department of Pediatrics, Faculty of Pediatrics, ∥Graduate Institute of Medicine, and ¶Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University; **Department of Medical Research, Kaohsiung Medical University Hospital; ††Center of Excellence for Environmental Medicine, Kaohsiung Medical University; and ‡‡Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan, ROC.
  1. Received September 17, 2011, and in revised form June 28, 2012.
  2. Accepted for publication June 28, 2012.
  3. Reprints: Chih-Hsing Hung, MD, PhD, Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung No. 68, Zhonghua 3rd Rd, Qianjin District, Kaohsiung City 801, Taiwan, ROC. E-mail: pedhung{at}gmail.com.
  4. Supported in part by grants from the 95-CCH-KMU-11, KMUH98-8G10, KMU-EM-99-4.1 (from the Center of Excellence for Environmental Medicine) and kmtth-100-014.

Abstract

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.

Key Words
  • chemokines
  • bronchial epithelial cell
  • long-acting beta 2 agonist
  • MAPKs
  • virus

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