Azelastine hydrochloride (Azeptin) inhibits peplomycin (PLM)-induced pulmonary fibrosis by contradicting the up-regulation of signal transduction.
Inhibition of peplomycin (PLM)-induced pulmonary fibrosis by azelastine hydrochloride (Azeptin) was examined using ICR mice, and the effects of both drugs on signal transduction were investigated. Microscopically, Azeptin (a total of 56 mg/kg for 28 days) suppressed pulmonary fibrosis in mice which received an i.p. injection of a total of 60 or 75 mg/kg PLM. In parallel with the microscopic findings, smaller amounts of collagen were synthesized in the lungs of Azeptin-injected mice. PLM enhanced the expression of interleukin-1 beta- and transforming growth factor-beta-mRNA in lungs. In contrast, Azeptin suppressed the expression. Compatible with these in vivo results, Azeptin and PLM contradictively regulated protein tyrosine phosphorylation and c-myc mRNA expression in human gingival and mouse pulmonary fibroblasts. In addition, NF-kappa B was activated by fibroblast treatment with 5 micrograms/ml PLM for 1 h, but intranuclear NF-kappa B was decreased by cell treatment with 10(-5) M Azeptin. From these results, it is concluded that Azeptin inhibits PLM-induced pulmonary fibrosis by antagonizing the up-regulation of signal transduction.
Yoneda
K
K
Department of Oral Surgery, Kochi Medical School, Japan.
Yamamoto
T
T
Ueta
E
E
Osaki
T
T
D000818:Animals; D016207:Cytokines / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D017663:Peplomycin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D010793:Phthalazines / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D016207:Cytokines; D016328:NF-kappa B; D010793:Phthalazines; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014443:Tyrosine; D017663:Peplomycin; C020976:azelastine