Effect of serum amyloid A1 (SAA1) on gene expression in primary murine macrophages
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PROVIDER: PRJNA649232 | ENA |
REPOSITORIES: ENA
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Project description:Macrophages are important regulators of the immune system and are critically involved in the pathophysiology of many diseases. Serum amlyoidosis is a protein misfolding disease which can follow chronic inflammatory conditions. Deposition of fibrils formed from serum amyloid A1 (SAA1) protein occurs systemically and can lead to severe or even fatal outcomes. Macrophages play a critical role in the misfolding and deposition of SAA1-derived fibrils and the role of macrophages in this context has been studied extensively. It is known that SAA1 can bind to some surface receptors on macrophages and it is taken up by the macrophages and metabolized in the lysosomes. On the other hand, the effect of SAA1 on macrophage physiology has been much less investigated so far. Therefore, we aim to investigate the effect of SAA1 on macrophage gene expression by gene microarray analysis. To this end, primary peritoneal macrophages from NMRI mice were treated with endotoxin-free recombinantly expressed full-length mSAA1 for 6 and 24 h and gene expression was analyzed.
2021-07-20 | GSE155278 | GEO
Project description:Metastasis is the key determinant of poor prognosis for advanced-stage NSCLC patients. Although an important contributor to metastasis is cross-talk between tumor-associated macrophages (TAMs) and tumor cells, its regulation is not fully understood. Expressed primarily in macrophages, scavenger receptor A1 (SR-A1) has been associated with lung tumorigenesis. Here, the mechanistic basis for the involvement of SR-A1 in lung cancer prognosis was investigated using population genetics, transcriptomics, and functional analyses. SR-A1 genetic variants were investigated for possible association with survival of advanced-stage NSCLC patients in the Harvard Lung Cancer Study cohort. Two SNPs (rs17484273, rs1484751) in SR-A1 were significantly associated with poor overall survival of NSCLC patients. Further, data from The Cancer Genome Atlas showed a considerable down-regulation of SR-A1 in lung tumor tissues. The association of SR-A1 with prognosis was validated in animal models in the context of lung cancer metastasis. Macrophages derived from SR-A1 knockout mice accelerated metastasis in a lung cancer mouse model. On the other hand, tumor cell seeding, migration, and invasion as well as macrophage accumulation in lung cancer tissue were enhanced in SR-A1 knockout mice. Furthermore, SR-A1 deficiency promoted up-regulation of serum amyloid A1 (SAA1) in macrophages, which appeared to be mediated by MAPK/Ikappa-B/NF-kappaB signaling. Further, SAA1 exposure promoted tumor cell invasion and macrophage migration in vitro and in vivo, but these effects were blocked by administration of an anti-SAA1 antibody. These findings suggest that SR-A1 may suppress lung cancer metastasis by down-regulating SAA1 production in macrophages.
2019-06-16 | GSE83473 | GEO
Project description:Sterile inflammation of the fetal membranes is an indispensable event of normal parturition. However, triggers of the sterile inflammation are not fully resolved. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver, which is believed to be implicated in the host inflammatory response to ensure early survival. Emerging evidence indicates that SAA1 can also be synthesized in extra-hepatic tissues including gestational tissues. Moreover, SAA1 synthesis is greatly enhanced in gestational tissues at parturition. Given the inflammatory actions of SAA1, we hypothesized that increased SAA1 synthesis locally in the fetal membranes may act as a humoral trigger of sterile inflammation of the fetal membranes at parturition. Here, by using transcriptomic sequencing and multiplex immunoassay, we found that multiple pathways related to chemotaxis were evoked by SAA1 in human amnion fibroblasts along with upregulation of a series of chemokines, particularly CCL3, CXCL6 and CCL20. Mechanistic studies showed that both toll-like receptor 4 (TLR4) and formyl peptide receptor 2 (FPR2) was involved in the induction of chemokines by SAA1. Moreover, SAA1-conditioned culture medium of amnion fibroblasts was capable of chemoattracting virtually all types of mononuclear leukocytes, particularly monocytes and dendritic cells, which reconciled well with the chemotactic activity of conditioned culture medium of amnion tissue explants collected from spontaneous labor. The infiltration of monocytes and dendritic cells to the fetal membranes at parturition was confirmed both morphologically with immunohistochemical staining and quantitatively with Western blotting. Additionally, SAA1 could also activate monocytes/macrophages and dendritic cells towards a proinflammatory phenotype. Conclusively, increased local SAA1 synthesis may trigger sterile inflammation of the fetal membranes at parturition by stimulating chemokine production initially in local cells resulting in increased chemotaxis of mononuclear leukocytes to the membranes to facilitate their transition towards the proinflammatory phenotype.
2025-11-10 | GSE217734 | GEO
Project description:Antifungal Activity of Mammalian Serum amyloid A1 against Candida albicans
| PRJNA528263 | ENA
Project description:Human serum amyloid A (SAA) is a major acute phase protein and shows a massive increase of concentration in plasma during inflammation. In the current study, we report that recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) have a potent antifungal activity against the major fungal pathogen Candida albicans. rhSAA1 binds to the cell surface of C. albicans and promotes cell aggregation. At high concentrations, rhSAA1 disrupts the membrane integrity and induces rapid cell death of C. albicans. Further investigation demonstrates that rhSAA1 targets on the cell wall adhesin Als3 of C. albicans. Inactivation of ALS3 in C. albicans leads to remarkably decreased cell aggregation and death upon rhSAA1 treatment, implying that Als3 plays a critical role in SAA1 sensing. Moreover, deletion of the ALS3 transcriptional regulators such as AHR1, BCR1, and EFG1 in C. albicans results in a similar effect on cell responses to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling analysis indicates that rhSAA1 has a remarkable impact on the expression of cell wall- and metabolism-related genes in C. albicans. Our finding of the antifungal activity of rhSAA1 against C. albicans expands the function of this protein and would provide new insights into the understanding of the host-Candida interaction during infections.
2019-09-01 | GSE128598 | GEO
Project description:Effect of HDL enriched with Serum Amyloid A1 (HDL+SAA1) on Gene Expression by Classical CD14+/CD16- Human Peripheral Blood Monocytes from Asthmatics
| PRJNA555747 | ENA
Project description:We report that the Serum Amyloid A protein, SAA1, is a novel, soluble co-factor able to promote pathogenic TH17 differentiation.
2019-12-05 | GSE132761 | GEO
Project description:Infection, sterile injury, and chronic inflammation trigger the acute phase response in order to re-establish homeostasis. This response includes production of positive acute phase proteins in the liver, such as members of the serum amyloid A (SAA) family. In humans the major acute phase SAAs comprise a group of closely related variants of SAA1 and SAA2. SAA1 was proven to be chemotactic for several leukocyte subtypes through activation of the G protein-coupled receptor FPRL1/FPR2. Several other biological activities of SAA1, such as cytokine induction, reported to be mediated via TLRs, have been debated recently. Especially commercial SAA1, recombinantly produced in Escherichia coli, was found to be contaminated with bacterial products confounding biological assays performed with this rSAA1. We purified rSAA1 by RP-HPLC to homogeneity, removing contaminants such as lipopolysaccharides, lipoproteins and formylated peptides, and re-assessed several biological activities attributed to SAA1 (chemotaxis, cytokine induction, MMP-9 release, ROS generation, and macrophage differentiation). The homogeneous rSAA1 (hrSAA1) lacked most cell-activating properties, but its leukocyte-recruiting capacity in vivo and it's in vitro synergy with other leukocyte attractants remained preserved. Furthermore, hrSAA1 maintained the ability to promote monocyte survival. This indicates that pure hrSAA1 retains its potential to activate FPR2, whereas TLR-mediated effects seem to be related to traces of bacterial TLR ligands in the E. coli-produced human rSAA1.
| S-EPMC7240019 | biostudies-literature
Project description:Determination of polymorphisms of SAA1 gene in cats
2025-12-20 | PRJEB105544 | EVA