Inflammation-responsive transcription factor SAF-1 activity is linked to the development of amyloid A amyloidosis

Alpana Ray, Arvind Shakya, Deepak Kumar, Merrill Benson, Bimal K. Ray

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Abundantly expressed serum amyloid A (SAA) protein under chronic inflammatory conditions gives rise to insoluble aggregates of SAA derivatives in multiple organs resulting in reactive amyloid A (AA) amyloidosis, a consequence of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, familial Mediterranean fever, and Castleman's disease. An inflammation-responsive transcription factor, SAF (for SAA activating factor), has been implicated in the sustained expression of amyloidogenic SAA under chronic inflammatory conditions. However, its role in the pathogenesis of AA amyloidosis has thus far remained obscure. In this paper we have shown that SAF-1, a major member of the SAF family, is abundantly present in human AA amyloidosis patients. To assess whether SAF-1 is directly linked to the pathogenesis of AA amyloidosis, we have developed a SAF-1 transgenic mouse model. SAF-1-overexpressing mice spontaneously developed AA amyloidosis at the age of 14 mo or older. Immunohistochemical analysis confirmed the nature of the amyloid deposits as an AA type derived from amyloidogenic SAA1. Furthermore, SAF-1 transgenic mice rapidly developed severe AA amyloidosis in response to azocasein injection, indicating increased susceptibility to inflammation. Also, during inflammation SAF-1 transgenic mice exhibited a prolonged acute phase response, leading to an extended period of SAA synthesis. Together, these results provide direct evidence that SAF-1 plays a key role in the development of AA amyloidosis, a consequence of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)2601-2609
Number of pages9
JournalJournal of Immunology
Volume177
Issue number4
StatePublished - Aug 15 2006
Externally publishedYes

Fingerprint

Activating Transcription Factors
Amyloidosis
Amyloid
Serum Amyloid A Protein
Inflammation
Transgenic Mice
Giant Lymph Node Hyperplasia
Familial Mediterranean Fever
Acute-Phase Reaction
Ankylosing Spondylitis
Amyloid Plaques
Crohn Disease
Rheumatoid Arthritis
Transcription Factors
Injections

ASJC Scopus subject areas

  • Immunology

Cite this

Inflammation-responsive transcription factor SAF-1 activity is linked to the development of amyloid A amyloidosis. / Ray, Alpana; Shakya, Arvind; Kumar, Deepak; Benson, Merrill; Ray, Bimal K.

In: Journal of Immunology, Vol. 177, No. 4, 15.08.2006, p. 2601-2609.

Research output: Contribution to journalArticle

Ray, Alpana ; Shakya, Arvind ; Kumar, Deepak ; Benson, Merrill ; Ray, Bimal K. / Inflammation-responsive transcription factor SAF-1 activity is linked to the development of amyloid A amyloidosis. In: Journal of Immunology. 2006 ; Vol. 177, No. 4. pp. 2601-2609.
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