Analysis of the gene expression profile activated by the CC chemokine ligand 5/RANTES and by lipopolysaccharide in human monocytes.
The gene expression profile induced by the CC chemokine ligand (CCL) 5/RANTES in human monocytes was examined using the oligonucleotide array technology. Of 5600 transcripts examined, 42 were consistently induced by CCL5, and none were suppressed. Chemokine-inducible transcripts could be clustered in functional groups, including selected cytokines and receptors (e.g., IL-1beta, CCL2/monocyte chemotactic protein-1, and the CCL5 receptor CCR1) and molecules involved in extracellular matrix recognition and digestion (e.g., CD44 splice transcripts, urokinase-type plasminogen activator receptor, matrix metalloprotease (MMP)-9, and MMP-19). Transcript expression, confirmed by quantitative real-time PCR analysis for selected genes, was associated with protein induction for some (e.g., CCL2), but not all (e.g., IL-1beta), transcripts examined. The chemokine-induced gene profile was distinct from that activated by LPS, a prototypic phagocyte activator. Although certain transcripts were stimulated by both agonists (e.g., IL-1beta and CCL2), others were induced only by either LPS (e.g., TNF-alpha and IL-6) or CCL5 (e.g., MMP-19) or were divergently regulated (e.g., CCR1). Thus, CCL5, a prototypic CC inflammatory chemokine, activates a restricted transcriptional program in monocytes distinct from that induced by the prototypic pathogen-derived proinflammatory stimulant LPS. Chemokine-induced chemokines production could represent a novel amplification loop of leukocyte recruitment, while a subset of chemokine-inducible transcripts could be involved in monocyte extravasation and tissue invasion.
Locati
Massimo
M
Istituto di Patologia Generale, Università degli Studi di Milano, Milan, Italy.
Deuschle
Ullrich
U
Massardi
Maria L
ML
Martinez
Fernando O
FO
Sironi
Marina
M
Sozzani
Silvano
S
Bartfai
Tamas
T
Mantovani
Alberto
A
D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology*; D019742:Chemokines, CC / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D018946:Chemokine CCL5; D019742:Chemokines, CC; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger