Contact with stimulated T cells up-regulates expression of peptidylarginine deiminase 2 and 4 by human monocytes

Autor: Céline Foulquier, Jean-Michel Dayer, Sylvie Ferrari-Lacraz, Mireille Sebbag, Rachel Chicheportiche, Guy Serre
Rok vydání: 2012
Předmět:
Interleukin-1beta/immunology
Arthritis
Rheumatoid/immunology
Macrophages/immunology/metabolism
Transcription
Genetic
RNA
Messenger/genetics/metabolism
Hydrolases
T-Lymphocytes
Clinical Biochemistry
Immunology
Interleukin-1beta
Arthritis
Stimulation
Lymphocyte Activation
Monocytes
Arthritis
Rheumatoid
Antigen
Downregulation and upregulation
Hydrolases/biosynthesis/genetics
Synovial Membrane/cytology/metabolism
Protein-Arginine Deiminase Type 2
Immunology and Allergy
Medicine
Humans
RNA
Messenger
Interferon-beta/immunology
Cells
Cultured
Autoantibodies
ddc:616
Fibroblasts/metabolism
Monocytes/immunology/metabolism
Autoantibodies/metabolism
business.industry
Macrophages
Synovial Membrane
Citrullination
Interferon-beta
T-Lymphocytes/immunology
Fibroblasts
Macrophage Activation
medicine.disease
Molecular biology
Isotype
Up-Regulation
PADI2
PADI4
Protein-Arginine Deiminases
business
Zdroj: European Cytokine Network, Vol. 23, No 2 (2012) pp. 36-44
ISSN: 1952-4005
1148-5493
Popis: Objective: The antigenic targets of the rheumatoid arthritis (RA)-associated autoantibodies to “citrullinated” proteins are generated following citrullination by a peptidylarginine deiminase (PAD). Of the five PAD isotypes, two – PAD2 and PAD4 – are expressed in RA synovial tissue. Within this tissue, the activation of macrophages and fibroblasts mediated by T-cell contact or driven by cytokines plays a prominent part in the pathogenesis. We wanted to determine whether cytokine stimulation and contact with T cells could play a role in PAD expression by peripheral blood monocytes and fibroblastic synoviocytes. Methods: Human monocytes and T lymphocytes were derived from the blood of healthy donors. HUT-78 cells and T lymphocytes were stimulated with PHA and PMA. Human synovial fibroblasts were isolated after surgical synoviectomy. The expression of PAD was determined by real-time PCR and immunoblot. Results: In monocytes, the PADI2 and PADI4 mRNAs were transiently up-regulated by contact with stimulated HUT-78 and/or T lymphocytes. Positive modulation of the PAD2 and PAD4 proteins were also observed upon contact with stimulated HUT-78 T cells. Stimulation by IL-1β or IFN-β did not modify the PADI2 and PADI4 mRNAs, but enhanced PAD4 protein expression. No isotype of PAD was detected at the mRNA or protein level in resting or stimulated synovial fibroblasts. Conclusion: Contact between stimulated T cells and monocyte-macrophages or cytokine-activated monocyte-macrophages constitutes a highly likely source of PAD2 and PAD4, which are observed in inflamed synovial tissues. In contrast, it is most unlikely that fibroblastic synoviocytes contribute to PAD expression in rheumatoid synovial membranes.
Databáze: OpenAIRE
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