Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Ann Rheum Dis. 2012 Feb;71(2):281-7. doi: 10.1136/annrheumdis-2011-200429. Epub 2011 Nov 9.

Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice.

Author information

  • 1Division of Rheumatology, University Hospitals of Geneva, Switzerland.

Abstract

OBJECTIVES:

To define the cell type (myeloid vs other cells) specific effect of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) deficiency on the acute inflammatory phase of arthritis.

METHODS:

Arthritis was induced by K/BxN serum transfer in wild-type (WT), IL-1Ra-deficient (IL-1Ra(-/-)) and conditional knockout mice. In the latter, IL-1Ra production was specifically targeted in myeloid cells (IL-1Ra(ΔM)) or in both hepatocytes and myeloid cells (IL-1Ra(ΔH+M)). Arthritis severity was clinically evaluated and ankle sections were scored for synovial inflammation and cartilage erosion. Quantitative RT-PCR, western blot and immunohistochemical analyses measured expression, localisation and cellular sources of the different IL-1Ra isoforms in arthritic joints.

RESULTS:

Total and myeloid cell-specific IL-1Ra deficiency was associated with increased arthritis severity, although disease incidence was similar to that of WT mice. Increased clinical scores were associated with exacerbated synovial inflammation. All IL-1Ra isoforms, except for intracellular (ic)IL-1Ra2, were expressed in arthritic joints of WT mice. In contrast, production of secreted (s)IL-1Ra and icIL-1Ra3 isoforms was markedly decreased in arthritic joints of both IL-1Ra(ΔM) and IL-1Ra(ΔH+M) mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts.

CONCLUSION:

Myeloid cell-derived IL-1Ra, including both sIL-1Ra and icIL-1Ra3 isoforms, controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis.

PMID:
22072017
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk