Requirement of type I interferon signaling for arthritis triggered by double-stranded RNA.

Abstract

OBJECTIVE:

Arthralgias and overt arthritides are often associated with viral infections. Viral infections expose the infected host to proinflammatory double-stranded RNA (dsRNA), which can cause joint inflammation and is a potent activator of interferon-alpha (IFNalpha). The aim of this study was to determine the role of IFNalpha and dsRNA-related signaling molecules in the onset of joint inflammation induced by viral dsRNA.

METHODS:

IFNalpha and different forms of RNA were injected into the knee joints of wild-type mice, mice lacking the type I interferon receptor (IFNAR(-/-)), and mice deficient in dsRNA-dependent protein kinase (PKR(-/-)). Histologic evidence of joint damage and the ability of splenocytes to produce cytokines in response to dsRNA or IFNalpha were assessed.

RESULTS:

Viral dsRNA, but not short single-stranded RNA, induced arthritis. The arthritis was aggravated by intracellular delivery of dsRNA. The expression of PKR was not mandatory for dsRNA-induced joint inflammation. In contrast, IFNalpha/beta signaling was important for dsRNA-induced joint inflammation because IFNAR(-/-) mice did not develop arthritis. Furthermore, intraarticular deposition of IFNalpha induced arthritis in PKR(-/-) and control mice, whereas IFNAR(-/-) mice were protected. The arthritogenic effect of IFNalpha was attenuated by in vivo depletion of monocyte/macrophages.

CONCLUSION:

Arthritis triggered by dsRNA is not dependent on the expression of the dsRNA-signaling molecule PKR (or Toll-like receptor 3, as previously shown), but is associated with the ability to produce type I IFN and is critically dependent on type I IFN receptor signaling. The intrinsic arthritogenic properties of IFNalpha implicate a role of this cytokine in joint manifestations triggered by various interferogenic stimuli.

• Authors: Mattias Magnusson, Fariba Zare, Andrej Tarkowski
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 54 Issue 1 Pg. 148-57 (Jan 2006) ISSN: 0004-3591 [Print] United States
• PMID: 16385510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-alpha
• RNA, Double-Stranded
• RNA, Viral

Topics

• Animals
• Arthritis (etiology, virology)
• Female
• Interferon-alpha (physiology)
• Mice
• RNA, Double-Stranded (physiology)
• RNA, Viral (physiology)