PARENT SESSION
1:30 PM to 3:30 PM
Saturday, April 20, 2002
Poster Session 2 Heat Shock Response and Mechanisms of Heat Damage
Room: Nevada 4-5
(MP02-19) Effect of tobacco smoke exposure on human airway epithelial cell stress responses.
Di, Yuan-Pu*,1,2,3, Harper, Richart1,2,3, Chemiel, Ken1, Yoneda, Ken1,2,3, 1 Center for Comparative Respiratory Biology and Medicine, Davis, Ca2 Department of Internal Medicine, Sacramento, CA3 Division of Pulmonary and Critical Care Medicine, Sacramento, CA
ABSTRACT-
The conducting airway epithelium provides the first line of protection and plays a vital role in pulmonary defense against various inhaled pollutants. Impaired or injured airway epithelium is frequently associated with environmental toxic exposure and subsequent stress conditions that are observed in pulmonary diseases, such as chronic bronchitis and chronic obstructive pulmonary diseases (COPD). Tobacco smoke (TS) exposure is one of the major environmental pollutants and risk factor that causes airway diseases. Our laboratory has been exploring the response of airway epithelial cells to environmental toxicant-induced lung injury, and recently has been examining the molecular events that occur after exposure of cells to TS. Using microarray screening, and subsequent confirmation by Northern blot analyses, the gene expression of several heat shock proteins (HSPs) such as HSP70, HSP40, and HSP28 are all elevated in primary cultured airway epithelial cells after tobacco smoke exposure. TS induced dose-dependent HSP expression, and the induced HSPs also protected cells from additional toxic exposure. In our system, TS exposure also increased of AP-1-dependent DNA binding and promoter activity. Co-expression of the dominant negative forms of ERK1, ERK2, JNK, and p38 are used to examine the signaling pathways that are involved in TS-induced promoter activities. Increased ERK1/ERK2 phosphorylation was observed by Western blot analyses. Tobacco smoke is a potent source of oxidants and oxidative stress is an important mechanism by which TS exerts its toxicity in the lung. It has been suggested that TS rapidly induces complex oxidant-mediated stress responses in both vascular endothelial cells and circulating monocytes. Here we report that TS induced stress responses in airway epithelium, which is one of the most sensitive target sites for toxic exposures. The increased heat shock proteins provide the functional role of cytoprotection under TS exposure and participate in maintaining protein integrity under oxidative stress conditions. NIH grants HL35635, TRDRP, and 1F32 HL09573 and ALA-CA RG-025L
KEYWORDS: heat shock proteins, tobacco smoke, airway epithelium, signaling mechanisms