Methylprednisolone and isoproterenol inhibit airway smooth muscle proliferation by separate and additive mechanisms.
To determine whether glucocorticoids and beta-adrenoceptor agonists act independently to inhibit airway smooth muscle (ASM) proliferation, the present study investigated the effects of methylprednisolone (MP) and isoproterenol (ISO) alone and in combination on leukotriene D4-induced ASM proliferation. MP and ISO had no effect on unstimulated ASM cell growth. In contrast, MP and ISO demonstrated dose-dependent inhibition of LTD4-induced proliferation, and the inhibitory effect was additive for combinations of MP and ISO. The competitive cAMP receptor antagonist, Rp-cAMPS, ablated the ISO-induced inhibition but had no affect on the inhibitory response to MP. In cells exposed to both ISO and MP, Rp-cAMPS attenuated the growth inhibition to levels achieved by MP alone. Accordingly, these findings demonstrate that glucocorticoids and beta-adrenergic agonists inhibit LTD4-induced ASM proliferation, and that their inhibitory effects are mediated by different signaling pathways.
Schramm
C M
CM
Pediatric Pulmonary Division, Univ. of Connecticut School of Medicine, Farmington 06030, USA. schramm@sun.uchc.edu
Omlor
G J
GJ
Quinn
L M
LM
Noveral
J P
JP
D000818:Animals; D002452:Cell Count / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits; D012137:Respiratory System / Q000187:drug effects*
D007545:Isoproterenol; D008775:Methylprednisolone