Lund University Publications

Balancing inflammation : the specific roles of serum amyloid A proteins in sterile and infectious diseases

• Mark

Mohanty, Tirthankar ^LU ; Miličević, Katarina ; Göthert, Henri ; Tillmann, Andreas ^LU ; Padra, Médea ^LU ; Papareddy, Praveen ^LU and Herwald, Heiko ^LU

Abstract

Serum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through
in vitro and
in vivo experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infectious conditions. Mechanistically, SAA proteins augment NF-κB signaling, driving pro and anti-inflammatory mediator production.
SAA
-/-
mice carrying a deletion of the
Saa1,
Saa2,
Saa3, and
Saa4 serum amyloid A genes have better survival rates in sterile sepsis but are more prone to bacterial sepsis than their
SAA
+/+
counterparts, emphasizing their dual functionality in... (More)

Serum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through
in vitro and
in vivo experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infectious conditions. Mechanistically, SAA proteins augment NF-κB signaling, driving pro and anti-inflammatory mediator production.
SAA
-/-
mice carrying a deletion of the
Saa1,
Saa2,
Saa3, and
Saa4 serum amyloid A genes have better survival rates in sterile sepsis but are more prone to bacterial sepsis than their
SAA
+/+
counterparts, emphasizing their dual functionality in immune regulation. Overexpression of
Saa1,
Saa2,
Saa3, and
Saa4 in macrophages enhances NF-κB-mediated pro-inflammatory cytokine production and bacterial clearance during infection. Together, our results show that SAA proteins are key modulators of inflammation, with distinct mechanisms tailored to sterile and infectious contexts.

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