Serum amyloid A induces interleukin‐6 in dermal fibroblasts via T oll‐like receptor 2, interleukin‐1 receptor‐associated kinase 4 and nuclear factor‐ κ B

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 protei...

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Veröffentlicht in:Immunology 2014-11, Vol.143 (3), p.331-340
Hauptverfasser: O'Reilly, Steven, Cant, Rachel, Ciechomska, Marzena, Finnigan, James, Oakley, Fiona, Hambleton, Sophie, van Laar, Jacob M.
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container_start_page 331
container_title Immunology
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creator O'Reilly, Steven
Cant, Rachel
Ciechomska, Marzena
Finnigan, James
Oakley, Fiona
Hambleton, Sophie
van Laar, Jacob M.
description 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 ( TLR s) promoting inflammation. This study addressed the role of SAA in initiating interleukin‐6 ( IL ‐6) production in dermal fibroblasts and the role of TLR 2 in this system. We show that SAA induces IL ‐6 secretion in healthy dermal fibroblasts and that blockade of TLR 2 with a neutralizing antibody to TLR 2 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‐ κ B‐mediated because blockade of nuclear factor‐ κ B reduced the induction. We also demonstrate that dermal fibroblasts express TLR 2; 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 TLR 2 signalling.
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title Serum amyloid A induces interleukin‐6 in dermal fibroblasts via T oll‐like receptor 2, interleukin‐1 receptor‐associated kinase 4 and nuclear factor‐ κ B
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