Mitogen-activated protein kinase pathway was significantly activated in human bronchial epithelial cells by nicotine.
Nicotine is potentially associated with the onset of chronic obstructive pulmonary disease (COPD) and lung cancer. To gain insights into the molecular mechanism underlying such nicotine-induced conditions, microarray- bioinformatics analysis was carried out in the present study to explore the gene expression profiles in human bronchial epithelial cells (HBECs) treated with 5 microM nicotine for 4, 8, and 10 h. Of 1,800 assessed genes overall, 260 (14.4%) were upregulated and 17 (0.9%) down regulated significantly. Gene ontology analysis demonstrated that most of the differentially expressed genes belonged to the category of molecular function, especially to the subcategories of enzyme activity. The integration of obtained information with bioinformatics tools in DAVID and KEGG databases indicated that the greatest number of overexpressed genes was involved in mitogen-activated protein kinase (MAPK) pathway. Membrane array analysis subsequently suggested that both extracellular signal-regulated kinase (ERK) 1/2 and c-Jun-NH(2)-terminal kinase (JNK) signalings but not p38 MAPK signaling were activated in response to nicotine. Pretreatment of HBECs with specific inhibitors against ERK 1/2 and JNK but not p38 could significantly inhibit nicotine-induced interleukin- 8 production. These results suggest that MAPK pathway may mediate the effect of nicotine through ERK 1/2 and JNK but not p38 in HBECs treated with nicotine.
Tsai
Jong-Rung
JR
MedicoGenomic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Chong
Inn-Wen
IW
Chen
Chung-Chi
CC
Lin
Shiu-Ru
SR
Sheu
Chau-Chyun
CC
Hwang
Jhi-Jhu
JJ
D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009538:Nicotine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis
D017931:DNA Primers; D018076:DNA, Complementary; D016209:Interleukin-8; D009538:Nicotine