TY - JOUR
T1 - Immunomodulatory effects of a low-dose clarithromycin-based macrolide solution pressurised metered dose inhaler
AU - Haghi, Mehra
AU - Saadat, Alessandro
AU - Zhu, Bing
AU - Colombo, Gaia
AU - King, Gregory
AU - Young, Paul M.
AU - Traini, Daniela
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Purpose The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells. Methods Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated. Results The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57×10-9± 2.32×10-9 cm.s-1, compared to 1.14×10-8±4.30×10-8 cm.s-1 for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2±0.5 ng.ml-1 clarithromycin treated vs. 7.7 ±0.8 ng.ml-1 control, respectively). Conclusions Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.
AB - Purpose The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells. Methods Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated. Results The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57×10-9± 2.32×10-9 cm.s-1, compared to 1.14×10-8±4.30×10-8 cm.s-1 for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2±0.5 ng.ml-1 clarithromycin treated vs. 7.7 ±0.8 ng.ml-1 control, respectively). Conclusions Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.
KW - Andersen cascade impactor
KW - Calu-3
KW - Epithelial transport
KW - Mucus
UR - http://www.scopus.com/inward/record.url?scp=84934979662&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/arc/DP120100251
U2 - 10.1007/s11095-014-1605-y
DO - 10.1007/s11095-014-1605-y
M3 - Article
C2 - 25537341
AN - SCOPUS:84934979662
SN - 0724-8741
VL - 32
SP - 2144
EP - 2153
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 6
ER -