A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells.
To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-kappaB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.
Huang
C Chris
CC
Centocor Research & Development, Incorporated, Malvern, Pennsylvania, USA. chuang4@cntus.jnj.com
Duffy
Karen E
KE
San Mateo
Lani R
LR
Amegadzie
Bernard Y
BY
Sarisky
Robert T
RT
Mbow
M Lamine
ML
D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007369:Interferon Inducers / Q000494:pharmacology*; D007372:Interferons / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D011070:Poly I-C / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000378:metabolism
D007369:Interferon Inducers; D016328:NF-kappa B; D051196:Toll-Like Receptor 3; D007372:Interferons; D011070:Poly I-C