Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogenic mechanisms

Connolly, Mary; Rooney, Peter R; McGarry, Trudy; Maratha, Ashwini; McCormick, Jennifer B.; Miggin, Sinéad M.; Veale, Douglas J.; Fearon, Ursula

doi:10.1136/annrheumdis-2015-207655

Cited by 53 publications

(42 citation statements)

References 53 publications

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“…However, Connolly et al . showed that SAA activated nuclear factor‐κB through Toll‐like receptor (TLR)2, not TLR4, in human embryonic kidney cells . Generally, NLRP3 is activated by TLR4 signaling.…”

Section: Discussionmentioning

confidence: 99%

Estradiol inhibits NLRP3 inflammasome in fibroblast‐like synoviocytes activated by lipopolysaccharide and adenosine triphosphate

Shi¹,

Zhao

et al. 2017

Int J of Rheum Dis

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Section: Discussionmentioning

confidence: 99%

Estradiol inhibits NLRP3 inflammasome in fibroblast‐like synoviocytes activated by lipopolysaccharide and adenosine triphosphate

Shi¹,

Zhao

et al. 2017

Int J of Rheum Dis

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“…The UAS scores were determined as daily (minimum = 0; and maximum = 6) and over 4 days (sum of the daily score values; minimum = 0; maximum = 24). The UAS was graded as: mild (0-8), moderate (9-16), and severe (17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Urticaria Activitymentioning

confidence: 99%

Serum amyloid A levels in acute and chronic urticaria

Lu¹,

Chen

Wang³

et al. 2019

An. Bras. Dermatol.

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Background: Serum amyloid A is an acute-phase protein. There is no available data regarding serum amyloid A levels in patients with acute (AU) and chronic urticaria (CU). oBjective: To investigate the association between serum amyloid A and urticaria. Methods: This was a case-control study of 81 patients who visited our Hospital between June and December 2016 with a diagnosis of urticaria. Eighty healthy controls (HC) who visited for routine health examination and physical checkups were recruited. Serum amyloid A and C-reactive protein levels were measured by automated methods. results: Serum amyloid A and C-reactive protein levels were significantly higher in AU (Serum amyloid A: 207.1 (6.7-439.0) mg/L; C-reactive protein: 16.0 (0.2-90.0) mg/L) and CU (Serum amyloid A: 6.5 (2.5-35.8) mg/L; C-reactive protein: 1.0 (0.1-16.0) mg/L) compared with HC (Serum amyloid A: 5.04 (2.0-9.1) mg/L; C-reactive protein: 1.2 (0.1-5.6) mg/L), and in AU compared with CU (all P<0.05). There were no differences between the CU and HC group. In CU, Serum amyloid A levels in those with moderate/severe urticaria (median, 16.4 (9.7-35.8) mg/L) were higher than in those with mild urticaria (median, 5.7 (2.5-9.5) mg/L) and HC (all P<0.05). Serum amyloid A and C-reactive protein levels exceeded the normal lab range in 90.7% and 72.1% patients with AU compared with 28.9% and 13.2% patients with CU, respectively. Significant positive correlations were found between serum amyloid A and C-reactive protein (r = 0.562, P < 0.001). study liMitations: There was no comparison between active disease and remission. conclusion: There was an association between serum amyloid A levels and urticaria. Higher serum amyloid A levels were associated with AU and more severe CU. Serum amyloid A may help to identify CU patients earlier.

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“…To date several receptors, including FPRL-1 [21], TLR2 [26,51] and TLR4 [28], receptor for advanced glycosylation end products (RAGE) [44], as well as class B scavenger receptors, SR-BI and CD36 [24,25,42], have been identified as SAA receptors that mediate its various functions. Our previous findings revealed that SR-BI and CD36, the most well–characterized members of SR-B family, could function as SAA receptors mediating its uptake and signaling in epithelial cells overexpressing these two proteins.…”

Section: Discussionmentioning

confidence: 99%

Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo

et al. 2017

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Serum amyloid A (SAA) is an acute phase protein with cytokine-like and chemotactic properties, that is markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This study provides new evidence that SR-BII, splice variant of SR-BI, could function as an SAA receptor mediating its uptake and pro-inflammatory signaling. The uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII-expressing HeLa cells when compared with mock-transfected cells. The levels of SAA-induced interleukin-8 secretion by hSR-BII-expressing HEK293 cells were also significantly (~3–3.5 fold) higher than those detected in control cells. Moderately enhanced levels of phosphorylation of all three mitogen-activated protein kinases, ERK1/2, and p38 and JNK, were observed in hSR-BII-expressing cells following SAA stimulation when compared with control wild type cells. Transgenic mice with pLiv-11-directed liver/kidney overexpression of hSR-BI or hSR-BII were used to assess the in vivo role of each receptor in SAA-induced pro-inflammatory response in these organs. Six hours after intraperitoneal SAA injection both groups of transgenic mice demonstrated markedly higher (~2-5-fold) expression levels of inflammatory mediators in the liver and kidney compared to wild type mice. Histological examinations of hepatic and renal tissue from SAA-treated mice revealed moderate level of damage in the liver of both transgenic but not in the wild type mice. Activities of plasma transaminases, biomarkers of liver injury, were also moderately higher in hSR-B transgenic mice when compared to wild type mice. Our findings identify hSR-BII as a functional SAA receptor that mediates SAA uptake and contributes to its pro-inflammatory signaling via the MAPKs-mediated signaling pathways.

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Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogenic mechanisms

Abstract: A-SAA is an endogenous ligand for TLR2, inducing pro-inflammatory effects in RA. Blocking the A-SAA/TLR2 interaction may be a potential therapeutic intervention in RA.

Cited by 53 publications

References 53 publications

Estradiol inhibits NLRP3 inflammasome in fibroblast‐like synoviocytes activated by lipopolysaccharide and adenosine triphosphate

Estradiol inhibits NLRP3 inflammasome in fibroblast‐like synoviocytes activated by lipopolysaccharide and adenosine triphosphate

Serum amyloid A levels in acute and chronic urticaria

Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo

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