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Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level
PloS one, 2013-01, Vol.8 (1), p.e54049-e54049
2013

Details

Autor(en) / Beteiligte
Titel
Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level
Ist Teil von
  • PloS one, 2013-01, Vol.8 (1), p.e54049-e54049
Ort / Verlag
United States: Public Library of Science
Erscheinungsjahr
2013
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
  • Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA. Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-α. Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1β after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions. We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients.
Sprache
Englisch
Identifikatoren
ISSN: 1932-6203
eISSN: 1932-6203
DOI: 10.1371/journal.pone.0054049
Titel-ID: cdi_plos_journals_1289061729
Format
–
Schlagworte
Analysis, ARNTL Transcription Factors - metabolism, Arthritis, Arthritis, Rheumatoid - genetics, Arthritis, Rheumatoid - metabolism, Arthritis, Rheumatoid - physiopathology, Binding sites, Biocompatibility, Biological clocks, Biology, Biomedical materials, BMAL1 protein, Chronic fatigue syndrome, Circadian Clocks - genetics, Circadian rhythm, Circadian rhythms, Clinical medicine, Clock gene, Corticosteroids, Cortisol, Fatigue, Fibroblasts, Fibroblasts - metabolism, Gene Expression, Gene Expression Regulation, Genes, Genomics, Glucocorticoids, Hospitals, Humans, Hypothalamic-pituitary-adrenal axis, Hypothalamus, Immunohistochemistry, Inflammation, Interleukin 6, Interleukin-1beta - genetics, Interleukin-1beta - metabolism, Interleukin-6 - genetics, Interleukin-6 - metabolism, Localization, Machinery and equipment, Medicine, Melatonin, Molecular machines, NPAS2 protein, Osteoarthritis, Osteoarthritis - genetics, Osteoarthritis - metabolism, Patients, Pituitary, Protein Transport, Proteins, Rheumatoid arthritis, Rheumatoid factor, Rheumatology, Rodents, Synovial membrane, Synovial Membrane - metabolism, Transcription factors, Tumor necrosis factor-α

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