Browse by author
Lookup NU author(s): Dr Steven O'Reilly, Rachel Cant, Dr Marzena Ciechomska, James Finnigan, Professor Fiona OakleyORCiD, Professor Sophie Hambleton, Professor Jaap Van Laar
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Systemic sclerosis is an autoimmune idiopathic connective tissue disease, characterized by vasculopathy, inflammation and fibrosis. There appears to be a link between inflammation and fibrosis, although the exact nature of the relationship is unknown. Serum amyloid A (SAA) is an acute-phase protein that is elevated up to 1000-fold in times of infection or inflammation. This acute-phase reactant, as well as being a marker of inflammation, may initiate signals in a cytokine-like manner, possibly through toll-like receptors (TLRs) promoting inflammation. This study addressed the role of SAA in initiating interleukin-6 (IL-6) production in dermal fibroblasts and the role of TLR2 in this system. We show that SAA induces IL-6 secretion in healthy dermal fibroblasts and that blockade of TLR2 with a neutralizing antibody to TLR2 or specific small interfering RNA attenuated the SAA-induced IL-6 secretion and that this was also mediated through the TLR adaptor protein IL-1 receptor-associated kinase 4. The effect is nuclear factor-kappa B-mediated because blockade of nuclear factor-kappa B reduced the induction. We also demonstrate that dermal fibroblasts express TLR2; this is functional and over-expressed in the fibroblasts of patients with systemic sclerosis. Taken together these data suggest that SAA is a danger signal that initiates IL-6 signalling in systemic sclerosis via enhanced TLR2 signalling.
Author(s): O'Reilly S, Cant R, Ciechomska M, Finnigan J, Oakley F, Hambleton S, van Laar JM
Publication type: Article
Publication status: Published
Journal: Immunology
Year: 2014
Volume: 143
Issue: 3
Pages: 331-340
Print publication date: 01/11/2014
Online publication date: 02/10/2014
Acceptance date: 24/01/2014
ISSN (print): 0019-2805
ISSN (electronic): 1365-2567
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1111/imm.12260
DOI: 10.1111/imm.12260
Altmetrics provided by Altmetric
