Experimental Model of Toxic Smoke Inhalation Injury

Research studies on wood smoke and other air pollution.

Experimental Model of Toxic Smoke Inhalation Injury

Postby Wilberforce » Wed Jan 02, 2013 6:54 pm

Inflammatory Role of AMP-Activated Protein Kinase Signaling in an Experimental Model of Toxic Smoke Inhalation Injury*
http://journals.lww.com/ccmjournal/Abst ... se.15.aspx
Perng, Diahn-Warng MD, PhD1,2; Chang, Tsung-Ming MS3; Wang, Jen-Ying MS3; Lee, Chih-Chieh MS3; Lu, Shing-Hwa MD, PhD2,4; Shyue, Song-Kun PhD5; Lee, Tzong-Shyuan DVM, PhD3; Kou, Yu Ru PhD3,6

Abstract

Objective: The molecular mechanisms underlying lung inflammation in toxic smoke inhalation injury are unknown. We investigated the signaling pathway responsible for the induction of interleukin 8 by wood smoke extract in lung epithelial cells and lung inflammation induced by wood smoke exposure in mice.

Design: A randomized, controlled study.

Setting: A research laboratory.

Interventions and Main Results: Exposure of primary human bronchial epithelial cells to wood smoke extract sequentially activated NADPH oxidase and increased intracellular reactive oxygen species level; activated AMP-activated protein kinase, extracellular signal-regulated kinase and Jun N-terminal kinase (two mitogen-activated protein kinases), and nuclear factor-?B and signal transducer and activator of transcription protein 3 (two transcription factors); and induced interleukin-8. Inhibition of NADPH oxidase activation with apocynin or siRNA targeting p47phox (a subunit of NADPH oxidase) attenuated the increased intracellular reactive oxygen species level, AMP-activated protein kinase activation, and interleukin-8 induction. Removal of intracellular reactive oxygen species by N-acetyl-cysteine reduced the activation of AMP-activated protein kinase, extracellular signal-regulated kinase and Jun N-terminal kinase, and interleukin-8 induction. Prevention of AMP-activated protein kinase activation by Compound C or AMP-activated protein kinase siRNA lessened the activation of Jun N-terminal kinase, extracellular signal-regulated kinase, nuclear factor-?B, signal transducer and activator of transcription protein 3 and interleukin-8 induction. Inhibition of Jun N-terminal kinase and extracellular signal-regulated kinase activation by inhibitors reduced the activation of nuclear factor-?B and signal transducer and activator of transcription protein 3 and interleukin-8 induction. Abrogation of nuclear factor-?B and signal transducer and activator of transcription protein 3 activation by inhibitors attenuated the interleukin-8 induction. Additionally, acute exposure of mice to wood smoke promoted AMP-activated protein kinase phosphorylation and expression of macrophage inflammatory protein 2 (an interleukin-8 homolog) in lung epithelial cells and lungs and lung inflammation, all of which were reduced by Compound C treatment.

Conclusions: Interleukin-8 induction by wood smoke extract in lung epithelial cells is mediated by novel NADPH oxidase-dependent, reactive oxygen species-sensitive AMP-activated protein kinase signaling with Jun N-terminal kinase and extracellular signal-regulated kinase as the downstream kinases and nuclear factor-?B and signal transducer and activator of transcription protein 3 as the downstream transcription factors. This AMP-activated protein kinase signaling is likely important for inducing lung inflammation with toxic smoke exposure in mice.
• The Surgeon General has determined that there is no safe level of exposure to ambient smoke!

• If you smell even a subtle odor of smoke, you are being exposed to poisonous and carcinogenic chemical compounds!

• Even a brief exposure to smoke raises blood pressure, (no matter what your state of health) and can cause blood clotting, stroke, or heart attack in vulnerable people. Even children experience elevated blood pressure when exposed to smoke!

• Since smoke drastically weakens the lungs' immune system, avoiding smoke is one of the best ways to prevent colds, flu, bronchitis, or risk of an even more serious respiratory illness, such as pneumonia or tuberculosis! Does your child have the flu? Chances are they have been exposed to ambient smoke!
User avatar
Wilberforce
 
Posts: 6093
Joined: Wed Jul 25, 2007 11:36 pm
Location: USA

Return to Particle Pollution Research

Who is online

Users browsing this forum: No registered users and 1 guest

cron