The effect of asthma therapeutics on signalling and transcriptional regulation of airway smooth muscle function.
Our knowledge of the multifunctional nature of airway smooth muscle (ASM) has expanded rapidly in the last decade, but the underlying molecular mechanisms and how current therapies for obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), affect these are still being elucidated. Our current knowledge has built on the pharmacology of human ASM contraction and relaxation established prior to that and which is reviewed in detail elsewhere in this issue. The advent of methods to isolate and culture ASM cells, especially human ASM cells, has made it possible to study how they may contribute to airway remodelling through their synthetic, proliferative, and migratory capacities. Now the underlying molecular mechanisms of ASM growth factor secretion, extracellular matrix (ECM) production, proliferation and migration, as well as contraction and relaxation, are being determined. A complex network of signalling pathways leading to gene transcription in ASM cells permits this functional plasticity in healthy and diseased airways. This review is an overview of the effects of current therapies, and some of those in development, on key signalling pathways and transcription factors involved in these ASM functions.
Ammit
Alaina J
AJ
Respiratory Research Group, Faculty of Pharmacy, University of Sydney, NSW, Australia. ajammit@pharm.usyd.edu.au
Burgess
Janette K
JK
Hirst
Stuart J
SJ
Hughes
J Margaret
JM
Kaur
Manminder
M
Lau
Justine Y
JY
Zuyderduyn
Suzanne
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D004205:Cromolyn Sodium / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017835:Nedocromil / Q000494:pharmacology / Q000627:therapeutic use; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D014157:Transcription Factors; D017835:Nedocromil; D004205:Cromolyn Sodium