@Article{ecn.2012.0303,
AUTHOR = {Sylvie Ferrari-Lacraz, Mireille Sebbag, Rachel Chicheportiche, Céline Foulquier, Guy Serre, Jean-Michel Dayer},
TITLE = {Contact with stimulated T cells up-regulates expression of peptidylarginine deiminase 2 and 4 by human monocytes},
JOURNAL = {European Cytokine Network},
VOLUME = {23},
YEAR = {2012},
NUMBER = {2},
PAGES = {36--44},
URL = {http://www.techscience.com/ECN/v23n2/65750},
ISSN = {1952-4005},
ABSTRACT = {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.},
DOI = {10.1684/ecn.2012.0303}
}