# Serum Amyloid A (SAA) induces transcription affecting inflammation

## TL;DR

Serum Amyloid A (SAA) can directly influence inflammation by altering gene expression in cells beyond immune cells.

## Contribution

The study shows SAA induces specific inflammatory transcripts in non-immune cells, suggesting an active role in inflammation.

## Key findings

- Exposure to SAA induces transcripts related to inflammation and NF-κB control in enteroids and HEK293 cells.
- SAA's effects on transcription suggest a direct role in cellular inflammation beyond macrophage activity.
- The findings imply SAA's evolutionary conservation is due to its role in primordial defense mechanisms.

## Abstract

The 104 aa protein Serum Amyloid A (SAA) is a prominent member of the acute phase response (APR) a remarkably conserved and stereotyped set of serum protein changes associated with inflammation and other stimuli. N-terminal fragments of SAA can form fibrils that accumulate in organs (where they are called “amyloidosis”). Recent reports have shown SAA involvement in inflammation, particularly with macrophages, consistent with its role as a “biomarker.” In contrast to this perception of passivity, we report that exposure to both N-terminal decapeptides and intact SAA monomers can induce multiple transcripts in both enteroids and HEK293 cells. The spectrum of transcripts prominently includes proteins related to inflammation and NF-κB control, specifically NFKB1A, TNFA1P3 and IER3. SAA thus can act directly through specific transcription to alter cellular physiology in cells outside the monocyte/macrophage lineage with direct effects on inflammation, likely helping explain its remarkable evolutionary conservation as part of primordial defense.