OBJECTIVE: To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. METHODS: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1-43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte-macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-gamma (IFN gamma; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a "reverse" IFN signature in AS patient macrophages, where IFN gamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFN gamma normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFN gamma gene was approximately 2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. CONCLUSIONS: Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking "reverse" IFN signature. Together with poor expression and responsiveness of the IFN gamma gene, these results suggest that there may be a relative defect in IFN gamma gene regulation, with autocrine consequences and implications for disease pathogenesis.
OBJECTIVE: To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. METHODS: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1-43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte-macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-gamma (IFN gamma; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a "reverse" IFN signature in AS patient macrophages, where IFN gamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFN gamma normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFN gamma gene was approximately 2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. CONCLUSIONS: Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking "reverse" IFN signature. Together with poor expression and responsiveness of the IFN gamma gene, these results suggest that there may be a relative defect in IFN gamma gene regulation, with autocrine consequences and implications for disease pathogenesis.
Authors: Franak M Batliwalla; Wentian Li; Christopher T Ritchlin; Xiangli Xiao; Max Brenner; Teresina Laragione; Tianmeng Shao; Robert Durham; Sunil Kemshetti; Edward Schwarz; Rodney Coe; Marlena Kern; Emily C Baechler; Timothy W Behrens; Peter K Gregersen; Pércio S Gulko Journal: Mol Med Date: 2005 Jan-Dec Impact factor: 6.354
Authors: Matthew J Turner; Dawn P Sowders; Monica L DeLay; Rajashree Mohapatra; Shuzhen Bai; Judith A Smith; Jaclyn R Brandewie; Joel D Taurog; Robert A Colbert Journal: J Immunol Date: 2005-08-15 Impact factor: 5.422
Authors: Dominique Baeten; Pieter Demetter; Claude A Cuvelier; Elli Kruithof; Nancy Van Damme; Martine De Vos; Eric M Veys; Filip De Keyser Journal: J Pathol Date: 2002-03 Impact factor: 7.996
Authors: Ingrid Fert; Nicolas Cagnard; Simon Glatigny; Franck Letourneur; Sébastien Jacques; Judith A Smith; Robert A Colbert; Joel D Taurog; Gilles Chiocchia; Luiza M Araujo; Maxime Breban Journal: Arthritis Rheumatol Date: 2014-04 Impact factor: 10.995