Clarithromycin inhibits overproduction of muc5ac core protein in murine model of diffuse panbronchiolitis.
Long-term treatment of macrolide antibiotics is considered an effective treatment for diffuse panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known that macrolides inhibit mucin production, the mechanism of the effect on mucin production is unclear. The aim of our study was to determine the production of muc5ac core protein, a major core protein of mucin in airway secretion, and the effect of clarithromycin treatment on such production in a mouse model mimicking DPB. Alcian blue-periodic acid-Schiff-positive cells were detected in the lungs of Pseudomonas aeruginosa-infected mice. Western blots of these mice showed muc5ac glycoprotein at day 1 and increased progressively from day 4 to day 14 after inoculation of bacteria. Clarithromycin (10 mg. kg-1. day-1 for 7 days) significantly reduced the muc5ac expression at both the mRNA and protein levels. To investigate the role of molecules upstream in muc5ac regulation, we examined the role of mitogen-activated protein kinase. Extracellular signal-regulated kinase 1/2 phosphorylation increased in the infected lung and decreased after treatment. Our results suggest that overproduction of muc5ac plays an important role in the pathogenesis of DPB and that clinical improvement following macrolide therapy seems to involve, at least in part, its inhibition of mucin overproduction, through modulation of intracellular signal transduction.
Kaneko
Yukihiro
Y
The Second Dept. of Internal Medicine, Nagasaki Univ. School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Yanagihara
Katsunori
K
Seki
Masafumi
M
Kuroki
Misuzu
M
Miyazaki
Yoshitsugu
Y
Hirakata
Yoichi
Y
Mukae
Hiroshi
H
Tomono
Kazunori
K
Kadota
Jun-Ichi
J
Kohno
Shigeru
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001988:Bronchiolitis / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D002452:Cell Count; D017291:Clarithromycin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D055271:Mucin 5AC; D009077:Mucins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology
D000900:Anti-Bacterial Agents; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D020928:Mitogen-Activated Protein Kinases; D017291:Clarithromycin