Asthma drugs counter-regulate interleukin-8 release stimulated by sodium sulfite in an A549 cell line.
BACKGROUND
Clinical manifestations suggest that air pollution may induce deterioration of respiratory health. Some air pollutants, including sulfite, may play a role in the exacerbation of asthma. Sulfites are formed at bronchial mucosa from inhaled sulfur dioxide. It has been previously reported that sodium sulfite (Na(2)SO(3)) has pro-inflammatory properties and enhances neutrophil adhesion to A549 cells. Interleukin-8 (IL-8) plays a critical role in attracting inflammatory cells and is an excellent marker of pulmonary cell activation. To date, there have not been any reports on the effect of asthma drugs on the suppression of IL-8 production induced by sulfite in A549 cells or the involvement of specific signal transduction pathways. Thus, our study assessed the effects of salmeterol, fluticasone, and montelukast on human epithelial lung cell inflammation as well as the inhibitors in different signal transduction pathways.


METHODS
A549 human lung epithelial cells were cultured under the following conditions: (1) treated with sodium sulfite (0, 100, 500, 1000, 2500 uM) for 16 hours; (2) cultured for 1 hour in the presence of SB203580, PD98059, SP600125, or wedeloactone, then co-incubated with sodium sulfite for another 16 hours; (3) cultured for 4 hours in the presence of salmeterol, fluticasone, or montelukast, then stimulated with sodium sulfite at a concentration of 1000 uM for 16 hours. We collected the supernatants from the above conditions and performed enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 concentration.


RESULTS
IL-8 production increased after treatment with sodium sulfite at 1000 to 2500 uM (p <or= 0.001). SB203580, PD98059, and wedeloactone decreased IL-8 production stimulated by Na(2)SO(3) (p < 0.01). Salmeterol, fluticasone, and montelukast significantly suppressed IL-8 secretion from sodium sulfite-stimulated A549 cells (p < 0.01).


CONCLUSIONS
Sodium sulfite has pro-inflammatory properties in vitro and can induce potent chemotactic factor IL-8 production. Possible signal transduction pathways required for IL-8 gene expression following exposure to sulfite are the NF-kappa B, ERK, and p-38-dependent pathways. Salmeterol, fluticasone, and montelukast all have inhibitory effects on sodium sulfite-induced IL-8 production in A549 cells.
Institute of Medicine, Chung-Shan Medical University, Taichung Veterans General Hospital, Taichung, Taiwan.
Ya-Fang
YF
Yang
Jeng-Yuan
JY
Hsu
Lin-Shien
LS
Fu
Yueh-Shan
YS
Weng
Jao-Jia
JJ
Chu
D000085:Acetates / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000068298:Fluticasone; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology; D011804:Quinolines / Q000494:pharmacology; D000068299:Salmeterol Xinafoate; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides; D013447:Sulfites / Q000633:toxicity*
D000085:Acetates; D000393:Air Pollutants; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D016209:Interleukin-8; D011804:Quinolines; D013440:Sulfides; D013447:Sulfites; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol; C025026:sodium sulfite