Lipopolysaccharide-stimulated responses in rat aortic endothelial cells by a systems biology approach.
The vascular endothelium plays an important role in regulating immune and inflammatory responses to resist pathogens infection. Although it has been known that lipopolysaccharide (LPS) is a critical inducer of sepsis or endotoxemia, the systematic responses of LPS-stimulation in endothelial cells (ECs) are still unclear. The present study aims to analyze the late-phase responses of LPS-induced rat aortic ECs by using systematic biology approaches, including rat cDNA microarray, 2-DE and MALDI-TOF MS/MS, and cytokine protein array. Furthermore, to improve the efficiency of analysis of the bulk systematic data of rat, we designed a set of bioinformatic tools to convert and integrate these rat data into the corresponding human genes or proteins IDs based on BioCarta, KEGG, and Gene Ontology databases. Using the systematic analysis, it was shown that LPS could promote some signaling or metabolic pathways as well as pathophysiologic phenomena of proliferation, atherogenesis, inflammation, and apoptosis through activated nuclear factor-kappaB pathway in ECs. Interestingly, ECs also activated the mediators of anti-inflammation, antiapoptosis, and antioxidation to protect themselves. Moreover, the expressions of altered genes, proteins, and their involvement in the hypothetical signaling pathway can provide further understanding of inflammation associated responses in ECs.
Tseng
Hsiang-Wen
HW
Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Juan
Hsueh-Fen
HF
Huang
Hsuan-Cheng
HC
Lin
John Yi-Chung
JY
Sinchaikul
Supachok
S
Lai
Tzi-Chung
TC
Chen
Chieh-Fu
CF
Chen
Shui-Tein
ST
Wang
Guei-Jane
GJ
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002478:Cells, Cultured; D016000:Cluster Analysis; D016207:Cytokines / Q000494:pharmacology; D030541:Databases, Genetic; D004730:Endothelium, Vascular / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008954:Models, Biological; D018448:Models, Immunological; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D049490:Systems Biology
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B