Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.

Full Abstract

Because IL-1beta plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC(-/-) mice showed reduced severity of AIA, decreased levels of synovial IL-1beta, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-gamma, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC(-/-) T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC(-/-) mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.

Author information

Author/s: Kolly, Laeticia (L); Karababa, Mahir (M); Joosten, Leo A B (LA); Narayan, Sharmal (S); Salvi, Roberto (R); Pétrilli, Virginie (V); Tschopp, Jurg (J); van den Berg, Wim B (WB); So, Alexander Kai-Lik (AK); Busso, Nathalie (N);

Affiliation: Service of Rheumatology, Département de l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois and University of Lausanne, University of Lausanne, Lausanne, Switzerland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 183 (issue 6) : pp 4003-12

Dates: Created 2009/09/03; Completed 2009/09/23;

PMID: 19717512, status: MEDLINE (last retrieval date: 9/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antigens - toxicity
Apoptosis Regulatory Proteins - deficiency
Arthritis, Experimental - etiology; pathology
Calcium-Binding Proteins - deficiency
Carrier Proteins - genetics
Caspase 1 - deficiency
Cell Proliferation

Associated Chemicals: Antigens (0) ; Apoptosis Regulatory Proteins (0) ; CIAS1 protein, mouse (0) ; Calcium-Binding Proteins (0) ; Carrier Proteins (0) ; Cytoskeletal Proteins (0) ; Ipaf protein, mouse (0) ; Multiprotein Complexes (0) ; Pycard protein, mouse (0) ; Caspase 1 (EC 3.4.22.36)

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