1. Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages
- Author
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Jumeau, Claire, Awad, Fawaz, Assrawi, Eman, Cobret, Laetitia, Duquesnoy, Philippe, Giurgea, Irina, Valeyre, Dominique, Grateau, Gilles, Amselem, Serge, Bernaudin, Jean-François, Karabina, Sonia-Athina, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
Lipopolysaccharides ,Physiology ,Interleukin-1beta ,Gene Expression ,Pathology and Laboratory Medicine ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Monocytes ,Dexamethasone ,White Blood Cells ,Animal Cells ,Immune Physiology ,Interleukin-1alpha ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,Immune Response ,Innate Immune System ,Healthy Volunteers ,Precipitation Techniques ,Liver ,Cytokines ,Medicine ,Cellular Types ,Research Article ,Immune Cells ,Science ,Immunology ,Research and Analysis Methods ,Signs and Symptoms ,Diagnostic Medicine ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genetics ,Immunoprecipitation ,Humans ,Immunoassays ,Secretion ,Inflammation ,Serum Amyloid A Protein ,Blood Cells ,Interleukin-6 ,Macrophages ,Biology and Life Sciences ,Cell Biology ,Molecular Development ,Gene Expression Regulation ,Immune System ,Immunologic Techniques ,Physiological Processes ,Developmental Biology - Abstract
International audience; 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.
- Published
- 2019
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