Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages

PLoS One. 2019 May 17;14(5):e0217005. doi: 10.1371/journal.pone.0217005. eCollection 2019.

Abstract

Circulating serum amyloid A (SAA) is increased in various inflammatory conditions. The human SAA protein family comprises the acute phase SAA1/SAA2, known to activate a large set of innate and adaptive immune cells, and the constitutive SAA4. The liver synthesis of SAA1/SAA2 is well-established but there is still an open debate on extrahepatic SAA expression especially in macrophages. We aimed to investigate the ability of human primary monocytes and monocyte-derived macrophages to express SAA1, SAA2 and SAA4 at both the transcriptional and protein levels, as previous studies almost exclusively dealt with monocytic cell lines. Monocytes and derived macrophages from healthy donors were stimulated under various conditions. In parallel with SAA, pro-inflammatory IL1A, IL1B and IL6 cytokine expression was assessed. While LPS alone was non-effective, a combined LPS/dexamethasone treatment induced SAA1 and to a lesser extent SAA2 transcription in human monocytes and macrophages. In contrast, as expected, pro-inflammatory cytokine expression was strongly induced following stimulation with LPS, an effect which was dampened in the presence of dexamethasone. Furthermore, in monocytes polarized towards a pro-inflammatory M1 phenotype, SAA expression in response to LPS/dexamethasone was potentiated; a result mainly seen for SAA1. However, a major discrepancy was observed between SAA mRNA and intracellular protein levels under the experimental conditions used. Our results demonstrate that human monocytes and macrophages can express SAA genes, mainly SAA1 in response to an inflammatory environment. While SAA is considered as a member of a large cytokine network, its expression in the monocytes-macrophages in response to LPS-dexamethasone is strikingly different from that observed for classic pro-inflammatory cytokines. As monocytes-macrophages are major players in chronic inflammatory diseases, it may be hypothesized that SAA production from macrophages may contribute to the local inflammatory microenvironment, especially when macrophages are compactly organized in granulomas as in sarcoidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dexamethasone / pharmacology
  • Gene Expression Regulation / drug effects
  • Healthy Volunteers
  • Humans
  • Inflammation / blood*
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-1alpha / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides / toxicity
  • Liver / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Serum Amyloid A Protein / genetics*

Substances

  • IL1A protein, human
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • SAA1 protein, human
  • SAA2 protein, human
  • SAA4 protein, human
  • Serum Amyloid A Protein
  • Dexamethasone

Grants and funding

Claire Jumeau was supported by a grant from the Doctoral School “Complexité du vivant”. Eman Assrawi was supported by a grant from the French government and An-Najah University (Palestine). Fawaz Awad was supported by a grant from the French government and Alquds University (Palestine) and from the “Fondation pour la Recherche Médicale” (FDT20130928419).