Analysis of the Gene Expression Profile Activated by the CC Chemokine Ligand 5/RANTES and by Lipopolysaccharide in Human Monocytes

• Published in: The Journal of immunology (1950) 2002-04, Vol.168 (7), p.3557-3562
• Main Authors: Locati, Massimo, Deuschle, Ullrich, Massardi, Maria L, Martinez, Fernando O, Sironi, Marina, Sozzani, Silvano, Bartfai, Tamas, Mantovani, Alberto
• Format: Article
• Language: English
• Subjects: CCL5 protein; Chemokine CCL5 - metabolism; Chemokine CCL5 - pharmacology; Chemokines, CC - metabolism; Gene Expression Profiling - methods; Gene Expression Regulation - immunology; Humans; Inflammation - genetics; Inflammation - immunology; Ligands; Lipopolysaccharides - pharmacology; Monocytes - immunology; Monocytes - metabolism; RANTES; RNA, Messenger - biosynthesis; Signal Transduction - genetics; Signal Transduction - immunology; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.7.3557

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.