Salbutamol inhibits lipopolysaccharide-induced inflammatory responses in rat peritoneal macrophages.
Acute and chronic inflammatory diseases are associated with the induction of inducible nitric oxide synthase (iNOS) and inducible heme oxygenase (HO-1). These inducible enzymes are up-regulated in macrophages subjected to inflammatory stimuli and oxidative stress. beta(2)-Adrenoceptor (AR) agonists, which function as bronchial dilators, are widely used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). We examined whether salbutamol, a classical beta(2)-AR agonist, inhibits the induction of proinflammatory cytokines and stress inducible proteins. Rat macrophages obtained from the abdominal cavity were incubated with lipopolysaccharide (LPS) with or without salbutamol. Induction by LPS of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was significantly inhibited (P < 0.05) by salbutamol treatment. Induction by LPS of iNOS mRNA and protein was also significantly inhibited (P < 0.05) by salbutamol. LPS-mediated increases in HO-1 mRNA and protein were not appreciably affected by salbutamol. One of the anti-inflammatory mechanisms of salbutamol was thus found to be inhibition of induction by LPS of extracellular stimulus-responsive kinase (ERK) 1/2 in macrophages. These findings suggest that salbutamol has the potential for use as an anti-inflammatory agent due to its suppression of LPS-induced TNF-alpha, and IL-6 and iNOS via ERK pathway without affecting HO-1 expression.
Toxicology Laboratory, Kissei Pharmaceutical Co., Ltd., Maki, Hotaka, Azumino-shi, Nagano, Japan. satoru_tanaka@pharm.kissei.co.jp
Satoru
S
Tanaka
Masaru
M
Tsutsui
Tomoyuki
T
Kishida
Shinji
S
Souma
Junji
J
Kuroda
Takemi
T
Yoshida
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048052:Mitogen-Activated Protein Kinase 3; D000420:Albuterol