TY - JOUR
T1 - Molecular mechanisms of lipopolysaccharide-caused induction of surfactant protein-A gene expression in human alveolar epithelial A549 cells
AU - Chuang, Chi Yuan
AU - Chen, Ta-Liang
AU - Chen, Ruei-Ming
PY - 2009/12/15
Y1 - 2009/12/15
N2 - Surfactant proteins (SPs) participate in the physiological and pathophysiological regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of SP-A and SP-D gene expressions in human alveolar epithelial A549 cells. Exposure of A549 cells to LPS increased SP-A mRNA synthesis in concentration and time-dependent manners without affecting SP-D mRNA production. LPS selectively enhanced translocation of transcription factor c-Jun from the cytoplasm to nuclei, but not nuclear factor kappa-B. In parallel, the DNA-binding activity of AP-1 was increased by LPS. Pretreatment of A549 cells with SP600125, an inhibitor of c-Jun N-terminal kinase, decreased c-Jun translocation, and significantly ameliorated LPS-induced SP-A mRNA production. Levels of toll-like receptor (TLR2) mRNA in A549 cells were time-dependently induced following LPS treatment. Application of TLR2 small interference (si)RNA into A549 cells significantly knocked-down the translation of this receptor, and simultaneously alleviated LPS-induced SP-A synthesis. Taken together, this study has shown that LPS selectively induces SP-A gene expression possibly through TLR2-mediated activation of c-Jun in human alveolar epithelial A549 cells.
AB - Surfactant proteins (SPs) participate in the physiological and pathophysiological regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of SP-A and SP-D gene expressions in human alveolar epithelial A549 cells. Exposure of A549 cells to LPS increased SP-A mRNA synthesis in concentration and time-dependent manners without affecting SP-D mRNA production. LPS selectively enhanced translocation of transcription factor c-Jun from the cytoplasm to nuclei, but not nuclear factor kappa-B. In parallel, the DNA-binding activity of AP-1 was increased by LPS. Pretreatment of A549 cells with SP600125, an inhibitor of c-Jun N-terminal kinase, decreased c-Jun translocation, and significantly ameliorated LPS-induced SP-A mRNA production. Levels of toll-like receptor (TLR2) mRNA in A549 cells were time-dependently induced following LPS treatment. Application of TLR2 small interference (si)RNA into A549 cells significantly knocked-down the translation of this receptor, and simultaneously alleviated LPS-induced SP-A synthesis. Taken together, this study has shown that LPS selectively induces SP-A gene expression possibly through TLR2-mediated activation of c-Jun in human alveolar epithelial A549 cells.
KW - Alveolar epithelial cells
KW - c-Jun
KW - Lipopolysaccharide
KW - Surfactant protein-A
KW - Toll-like receptor 2
UR - http://www.scopus.com/inward/record.url?scp=70449528492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449528492&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2009.08.015
DO - 10.1016/j.toxlet.2009.08.015
M3 - Article
C2 - 19712733
AN - SCOPUS:70449528492
SN - 0378-4274
VL - 191
SP - 132
EP - 139
JO - Toxicology Letters
JF - Toxicology Letters
IS - 2-3
ER -