JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Wood smoke extract promotes both apoptosis and proliferation in rat alveolar epithelial type II cells: the role of oxidative stress and heme oxygenase-1.

Critical Care Medicine 2008 September
OBJECTIVE: Inhalation of toxic smoke causes oxidant lung injury. Alveolar epithelial type II cells are important in the re-epithelialization of alveolar walls after lung injury. We investigated the responses of alveolar epithelial type II cells to insult by wood smoke extract, and we identified the role of reactive oxygen species and heme oxygenase-1 (an oxidative stress protein) in these responses.

DESIGN: A randomized, controlled study.

SETTING: A research laboratory.

SUBJECTS: Cultured rat L2 and primary alveolar epithelial type II cells.

INTERVENTIONS AND MAIN RESULTS: Exposure of L2 alveolar epithelial type II cells to smoke extract (60 microg/mL) caused increases in reactive oxygen species, mitogen-activated protein kinases phosphorylation, heme oxygenase-1 expression, apoptosis, proliferation and cell population, all of which were largely reduced by N-acetylcysteine (an antioxidant). Additionally, the smoke extract-induced heme oxygenase-1 induction was significantly attenuated by mitogen-activated protein kinases inhibitors, by small interfering RNA targeting mitogen-activated protein kinases or by N-acetylcysteine. Furthermore, knockdown of heme oxygenase-1 by small interfering RNA prevented heme oxygenase-1 induction whereas increasing smoke extract-induced apoptosis and suppressing smoke extract-induced proliferation. Conversely, cobalt protoporphyrin IX (a heme oxygenase-1 inducer) amplified heme oxygenase-1 induction while suppressing smoke extract-induced apoptosis and augmenting smoke extract-induced proliferation. Consequently, the smoke extract-induced increase in cell population was changed into a decrease by heme oxygenase-1 small interfering RNA, but was further elevated by cobalt protoporphyrin IX. Smoke extract also caused increases in heme oxygenase-1 expression, apoptosis, proliferation and cell population in primary alveolar epithelial type II cells, and heme oxygenase-1 small interfering RNA similarly augmented smoke extract-induced apoptosis and suppressed smoke extract-induced proliferation in these primary cells.

CONCLUSIONS: Smoke extract increases intracellular reactive oxygen species, which up-regulates heme oxygenase-1 via the mitogen-activated protein kinase pathways and also promotes both apoptosis and proliferation in rat alveolar epithelial type II cells. Additionally, smoke extract-induced heme oxygenase-1 induction counteracts smoke extract-induced apoptosis, but mediates smoke extract-induced proliferation, resulting in a net increase in cell population. Thus, in response to oxidant smoke insult, alveolar epithelial type II cells have evolved an adaptive mechanism involving heme oxygenase-1 that increases their cell population, presumably to help them perform their function of re-epithelialization following lung injury.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app