Anti-inflammatory effects of β2 adrenergic receptor agonists in experimental acute lung injury.
These studies were undertaken to extend emerging evidence that β(2) adrenergic receptor (β(2)AR) agonists, in addition to their bronchorelaxing effects, may have broad anti-inflammatory effects in the lung following onset of experimental acute lung injury (ALI). Young male C57BL/6 mice (25 g) developed ALI following airway deposition of bacterial LPS or IgG immune complexes in the absence or presence of appropriate stereoisomers (enantiomers) of β(2)AR agonists, albuterol or formoterol. Endpoints included albumin leak into lung and buildup of polymorphonuclear neutrophils and cytokines/chemokines in bronchoalveolar fluids. Both β(2)AR agonists suppressed lung inflammatory parameters (IC(50)=10(-7) M). Similar effects of β(2)AR agonists on mediator release were found when mouse macrophages were stimulated in vitro with LPS. The protective effects were associated with reduced activation (phosphorylation) of JNK but not of other signaling proteins. Collectively, these data suggest that β(2)AR agonists have broad anti-inflammatory effects in the setting of ALI. While β(2)AR agonists suppress JNK activation, the extent to which this can explain the blunted lung inflammatory responses in the ALI models remains to be determined.
The University of Michigan Medical School, Department of Pathology, 1301 Catherine Rd. Box 5602, Ann Arbor, MI 48109-5602, USA.
Markus
M
Bosmann
Jamison J
JJ
Grailer
Ketong
K
Zhu
Michael A
MA
Matthay
J Vidya
JV
Sarma
Firas S
FS
Zetoune
Peter A
PA
Ward
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents