Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs: possible role of interleukin-8
Inoue, H; Aizawa, H; Nakano, H; Matsumoto, K; Kuwano, K; Nadel, JA; Hara, N
HERO ID
12005
Reference Type
Journal Article
Year
2000
Language
English
PMID
| HERO ID | 12005 |
|---|---|
| In Press | No |
| Year | 2000 |
| Title | Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs: possible role of interleukin-8 |
| Authors | Inoue, H; Aizawa, H; Nakano, H; Matsumoto, K; Kuwano, K; Nadel, JA; Hara, N |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 161 |
| Issue | 1 |
| Page Numbers | 249-256 |
| Abstract | Nitric oxide (NO) is increased in exhaled air of asthmatics. We hypothesized that endogenous NO contributes to airway inflammation and hyperresponsiveness, and that interleukin-8 (IL-8) might be involved in this mechanism. In human transformed bronchial epithelial cells in vitro, NO donors increased IL-8 production dose-dependently. In addition, tumor necrosis factor-"alpha" (TNF-"alpha") plus IL-1"beta" plus interferon-"gamma" (IFN-"gamma") increased IL-8 in culture supernatant of epithelial cells; the combination of NO synthase (NOS) inhibitors, aminoguanidine (AG) plus NG-nitro-L-arginine methyl ester (L-NAME) attenuated the cytokine-induced IL-8 production in epithelial cells. In guinea pigs in vivo, ozone exposure induced airway hyperresponsiveness to acetylcholine and increased neutrophils in bronchoalveolar lavage fluid (BALF), and these changes persisted for at least 5 h. Pretreatment with NOS inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NOS inhibitors also attenuated the increases of nitrite/nitrate levels in BALF and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8. |
| Doi | 10.1164/ajrccm.161.1.9804096 |
| Pmid | 10619828 |
| Wosid | WOS:000084820200041 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | ECRIB.Am. J. Respir. Crit. Care Med. 161: 249-256. |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |