Suppressive effects of formoterol and salmeterol on eotaxin-1 in bronchial epithelial cells.
Eotaxin-1 (CCL11), an eosinophil-specific C-C chemokine, is a potent chemoattractant for mobilization of eosinophils into airways after allergic stimulation. Eotaxin-1 recruits eosinophils into inflammatory sites, and may play a role in the pathogenesis of asthma. Formoterol and salmeterol are two inhaled long acting beta(2) adrenoceptor agonists (LABAs), widely used for the local treatment of asthma. However, little is known about their effects on the eotaxin-1 expression of bronchial epithelial cells. BEAS-2B cells were stimulated by adding IL-4 with or without 2 h pre-treatment of formoterol or salmeterol. The protein and mRNA expression of eotaxin-1 were measured by ELISA assay and real-time PCR, respectively. Effects of formoterol and salmeterol on nuclear and cytosolic pSTAT-6 expression were evaluated by Western blot and immunofluorescence study. Formoterol and salmeterol (10(-7)-10(-10) m) significantly down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. A specific beta(2) adrenoceptor antagonist (ICI 118,551) reversed their suppression of eotaxin-1 production. Forskolin, an cAMP activator, could also suppress the expression of eotaxin-1 by IL-4 in a dose dependent manner (10(-7)-10(-10 )m). The western blot and immunofluorescence studies demonstrated that formoterol 10(-7 )m suppressed the nuclear expression of pSTAT-6. Formoterol and salmeterol, two inhaled long-acting beta(2) agonists, down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. The effect was mediated via the beta(2) adrenoceptor, and cAMP. Formoterol significantly down-regulated pSTAT6 at higher concentration, and further turned off the IL-4 signaling pathway.
Chu
Yu-Te
YT
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Tai-Tsung
TT
Jong
Yuh-Jyh
YJ
Kuo
Po-Lin
PL
Lee
Hsi-Ming
HM
Lee
Min-Sheng
MS
Chang
Hui-Wen
HW
Hung
Chih-Hsing
CH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D054413:Chemokine CCL11 / Q000032:analysis / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000378:metabolism; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D004983:Ethanolamines; D011412:Propanolamines; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D005576:Colforsin; D015847:Interleukin-4; C026777:ICI 118551; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate