Role of NOS2 in pulmonary injury and repair in response to bleomycin
| Parent link: | Free Radical Biology and Medicine: International Interdisciplinary Journal Vol. 91.— 2016.— [P. 293–301] |
|---|---|
| Institution som forfatter: | |
| Andre forfattere: | , , , , , , |
| Summary: | Title screen Nitric oxide (NO) is derived from multiple isoforms of the Nitric Oxide Synthases (NOSs) within the lung for a variety of functions; however, NOS2-derived nitrogen oxides seem to play an important role in inflammatory regulation. In this study, we investigate the role of NOS2 in pulmonary inflammation/fibrosis in response to intratracheal bleomycin instillation (ITB) and to determine if these effects are related to macrophage phenotype. Systemic NOS2 inhibition was achieved by administration of 1400 W, a specific and potent NOS2 inhibitor, via osmotic pump starting six days prior to ITB. 1400 W administration attenuated lung inflammation, decreased chemotactic activity of the broncheoalveolar lavage (BAL), and reduced BAL cell count and nitrogen oxide production. S-nitrosylated SP-D (SNO-SP-D), which has a pro-inflammatory function, was formed in response to ITB; but this formation, as well as structural disruption of SP-D, was inhibited by 1400 W. mRNA levels of IL-1β, CCL2 and Ptgs2 were decreased by 1400 W treatment. In contrast, expression of genes associated with alternate macrophage activation and fibrosis Fizz1, TGF-β and Ym-1 was not changed by 1400 W. Similar to the effects of 1400 W, NOS2−/− mice displayed an attenuated inflammatory response to ITB (day 3 and day 8 post-instillation). The DNA-binding activity of NF-κB was attenuated in NOS2−/− mice; in addition, expression of alternate activation genes (Fizz1, Ym-1, Gal3, Arg1) was increased. This shift towards an increase in alternate activation was confirmed by western blot for Fizz-1 and Gal-3 that show persistent up-regulation 15 days after ITB. In contrast arginase, which is increased in expression at 8 days post ITB in NOS2−/−, resolves by day 15. These data suggest that NOS2, while critical to the development of the acute inflammatory response to injury, is also necessary to control the late phase response to ITB. Режим доступа: по договору с организацией-держателем ресурса |
| Udgivet: |
2016
|
| Fag: | |
| Online adgang: | http://dx.doi.org/10.1016/j.freeradbiomed.2015.10.417 |
| Format: | Electronisk Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=650331 |
MARC
| LEADER | 00000naa0a2200000 4500 | ||
|---|---|---|---|
| 001 | 650331 | ||
| 005 | 20250313094110.0 | ||
| 035 | |a (RuTPU)RU\TPU\network\15549 | ||
| 035 | |a RU\TPU\network\15544 | ||
| 090 | |a 650331 | ||
| 100 | |a 20161003d2016 k||y0rusy50 ba | ||
| 101 | 0 | |a eng | |
| 135 | |a drcn ---uucaa | ||
| 181 | 0 | |a i | |
| 182 | 0 | |a b | |
| 200 | 1 | |a Role of NOS2 in pulmonary injury and repair in response to bleomycin |f G. Guo [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: p. 300-301 (49 tit.)] | ||
| 330 | |a Nitric oxide (NO) is derived from multiple isoforms of the Nitric Oxide Synthases (NOSs) within the lung for a variety of functions; however, NOS2-derived nitrogen oxides seem to play an important role in inflammatory regulation. In this study, we investigate the role of NOS2 in pulmonary inflammation/fibrosis in response to intratracheal bleomycin instillation (ITB) and to determine if these effects are related to macrophage phenotype. Systemic NOS2 inhibition was achieved by administration of 1400 W, a specific and potent NOS2 inhibitor, via osmotic pump starting six days prior to ITB. 1400 W administration attenuated lung inflammation, decreased chemotactic activity of the broncheoalveolar lavage (BAL), and reduced BAL cell count and nitrogen oxide production. S-nitrosylated SP-D (SNO-SP-D), which has a pro-inflammatory function, was formed in response to ITB; but this formation, as well as structural disruption of SP-D, was inhibited by 1400 W. mRNA levels of IL-1β, CCL2 and Ptgs2 were decreased by 1400 W treatment. In contrast, expression of genes associated with alternate macrophage activation and fibrosis Fizz1, TGF-β and Ym-1 was not changed by 1400 W. Similar to the effects of 1400 W, NOS2−/− mice displayed an attenuated inflammatory response to ITB (day 3 and day 8 post-instillation). The DNA-binding activity of NF-κB was attenuated in NOS2−/− mice; in addition, expression of alternate activation genes (Fizz1, Ym-1, Gal3, Arg1) was increased. This shift towards an increase in alternate activation was confirmed by western blot for Fizz-1 and Gal-3 that show persistent up-regulation 15 days after ITB. In contrast arginase, which is increased in expression at 8 days post ITB in NOS2−/−, resolves by day 15. These data suggest that NOS2, while critical to the development of the acute inflammatory response to injury, is also necessary to control the late phase response to ITB. | ||
| 333 | |a Режим доступа: по договору с организацией-держателем ресурса | ||
| 461 | |t Free Radical Biology and Medicine |o International Interdisciplinary Journal | ||
| 463 | |t Vol. 91 |v [P. 293–301] |d 2016 | ||
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 701 | 1 | |a Guo |b G. |g Guo | |
| 701 | 1 | |a Atochina |b E. N. |c biophysicist |c Director of RASA Center in Tomsk of Tomsk Polytechnic University |f 1963- |g Elena Nikolaevna |3 (RuTPU)RU\TPU\pers\37356 |9 20274 | |
| 701 | 1 | |a Abramova |b H. |g Helen | |
| 701 | 1 | |a George |b B. |g Blessy | |
| 701 | 1 | |a Manoj |b V. |g Veleeparambil | |
| 701 | 1 | |a Scott |b P. |g Pamela | |
| 701 | 1 | |a Gow |b A. |g Andrew | |
| 712 | 0 | 2 | |a Национальный исследовательский Томский политехнический университет |b Управление проректора по научной работе и инновациям |b Центр RASA в Томске |3 (RuTPU)RU\TPU\col\21814 |9 28135 |
| 801 | 2 | |a RU |b 63413507 |c 20161003 |g RCR | |
| 856 | 4 | |u http://dx.doi.org/10.1016/j.freeradbiomed.2015.10.417 | |
| 942 | |c CF | ||