title: Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis.
abstract: Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).
authors.affiliation: Rheumatoid Arthritis Disease Biology Department, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK. inma_rioja@yahoo.com
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Rioja
authors.forename: Chris L
authors.initials: CL
authors.lastname: Clayton
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Graham
authors.forename: Paul F
authors.initials: PF
authors.lastname: Life
authors.forename: Marion C
authors.initials: MC
authors.lastname: Dickson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002473:Cell Wall / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007270:Injections, Intra-Articular; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010457:Peptidoglycan / Q000008:administration & dosage / Q000633:toxicity; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000633:toxicity; D040641:Quantitative Trait Loci; D051381:Rats; D011917:Rats, Inbred Lew; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000737:chemistry*; D013583:Synovial Membrane / Q000378:metabolism; D013643:Tarsus, Animal
chemical_list: D018925:Chemokines; D016207:Cytokines; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D018121:Receptors, Cytokine