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Effect of serum amyloid A1 treatment on global gene expression in THP-1-derived macrophages

Inflammation Research volume 61, pages 391–398 (2012)Cite this article

Abstract

Objective

To investigate the effect of serum amyloid A1 (SAA1) on global gene expression in macrophages derived from THP-1 monocytes.

Materials and methods

Global genetic expression in THP-1-derived macrophages was determined using Illumina HT-12 microarray chips and the results were validated by real-time PCR. Cytokine levels in cellular supernatant were quantified by ELISA.

Results

In total, 55 genes were upregulated with fold difference greater than two when THP-1-derived macrophages were incubated with SAA1 for 8 h. SAA1 is a strong cytokine inducer with significant upregulation of chemokines CCL1, CCL3, and CCL4 and this was confirmed by both real-time PCR and ELISA quantification. SAA1 also promotes the upregulation of genes involved in phagocytosis, anti-apoptosis, and tissue remodeling.

Conclusions

SAA1 appears to play an important role during the immune response and in chronic inflammatory diseases through the stimulation of genes involved in cytokine production, phagocytosis, and anti-apoptosis.

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Fig. 1

References

  1. Shah C, Hari-Dass R, Raynes JG. Serum amyloid A is an innate immune opsonin for Gram-negative bacteria. Blood. 2006;108:1751–7.

    PubMed  Article  CAS  Google Scholar 

  2. Malle E, Steinmetz A, Raynes JG. Serum amyloid A (SAA): an acute phase protein and apolipoprotein. Atherosclerosis. 1993;102:131–46.

    PubMed  Article  CAS  Google Scholar 

  3. Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, et al. Acute-phase serum amyloid A: an inflammatory adipokine, potential link between obesity, its metabolic complications. PLoS Med. 2006;3:e287.

    PubMed  Article  Google Scholar 

  4. Poitou C, Divoux A, Faty A, Tordjman J, Hugol D, Aissat A, et al. Role of serum amyloid A in adipocyte-macrophage cross talk and adipocyte cholesterol efflux. J Clin Endocrinol Metab. 2009;94:1810–7.

    PubMed  Article  CAS  Google Scholar 

  5. Kumon Y, Suehiro T, Hashimoto K, Nakatani K, Sipe JD. Local expression of acute phase serum amyloid A mRNA in rheumatoid arthritis synovial tissue and cells. J Rheumatol. 1999;26:785–90.

    PubMed  CAS  Google Scholar 

  6. Cho WC, Yip TT, Cheng WW, Au JS. Serum amyloid A is elevated in the serum of lung cancer patients with poor prognosis. Br J Cancer. 2010;102:1731–5.

    PubMed  Article  CAS  Google Scholar 

  7. Kotani K, Satoh N, Kato Y, Araki R, Koyama K, Okajima T, et al. A novel oxidized low-density lipoprotein marker, serum amyloid A-LDL, is associated with obesity and the metabolic syndrome. Atherosclerosis. 2009;204:526–31.

    PubMed  Article  CAS  Google Scholar 

  8. Ramankulov A, Lein M, Johannsen M, Schrader M, Miller K, Loening SA, et al. Serum amyloid A as indicator of distant metastases but not as early tumor marker in patients with renal cell carcinoma. Cancer Lett. 2008;269:85–92.

    PubMed  Article  CAS  Google Scholar 

  9. Kumon Y, Loose LD, Birbara CA, Sipe JD. Rheumatoid arthritis exhibits reduced acute phase and enhanced constitutive serum amyloid A protein in synovial fluid relative to serum. A comparison with C-reactive protein. J Rheumatol. 1997;24:14–9.

    PubMed  CAS  Google Scholar 

  10. Van Lenten BJ, Wagner AC, Navab M, Anantharamaiah GM, Hama S, Reddy ST, et al. Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits. J Lipid Res. 2007;48:2344–53.

    PubMed  Article  Google Scholar 

  11. Lewis KE, Kirk EA, McDonald TO, Wang S, Wight TN, O’Brien KD, et al. Increase in serum amyloid A evoked by dietary cholesterol is associated with increased atherosclerosis in mice. Circ. 2004;110:540–5.

    Article  CAS  Google Scholar 

  12. Liao F, Lusis AJ, Berliner JA, Fogelman AM, Kindy M, de Beer MC, et al. Serum amyloid A protein family. Differential induction by oxidized lipids in mouse strains. Arterioscler Thromb. 1994;14:1475–9.

    PubMed  Article  CAS  Google Scholar 

  13. Meek RL, Urieli-Shoval S, Benditt EP. Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid A function. Proc Natl Acad Sci USA. 1994;91:3186–90.

    PubMed  Article  CAS  Google Scholar 

  14. Pruzanski W, de Beer FC, de Beer MC, Stefanski E, Vadas P. Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2. Biochem J. 1995;309(Pt 2):461–4.

    PubMed  CAS  Google Scholar 

  15. Mitchell TI, Coon CI, Brinckerhoff CE. Serum amyloid A (SAA3) produced by rabbit synovial fibroblasts treated with phorbol esters or interleukin 1 induces synthesis of collagenase and is neutralized with specific antiserum. J Clin Invest. 1991;87:1177–85.

    PubMed  Article  CAS  Google Scholar 

  16. Migita K, Kawabe Y, Tominaga M, Origuchi T, Aoyagi T, Eguchi K. Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts. Lab Invest. 1998;78:535–9.

    PubMed  CAS  Google Scholar 

  17. Song C, Hsu K, Yamen E, Yan W, Fock J, Witting PK, et al. Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes. Atherosclerosis. 2009;207:374–83.

    PubMed  Article  CAS  Google Scholar 

  18. Zimlichman S, Danon A, Nathan I, Mozes G, Shainkin-Kestenbaum R. Serum amyloid A, an acute phase protein, inhibits platelet activation. J Lab Clin Med. 1990;116:180–6.

    PubMed  CAS  Google Scholar 

  19. Tam SP, Kisilevsky R, Ancsin JB. Acute-phase-HDL remodeling by heparan sulfate generates a novel lipoprotein with exceptional cholesterol efflux activity from macrophages. PLoS One. 2008;3:e3867.

    PubMed  Article  Google Scholar 

  20. Yamada T, Wada A, Itoh Y, Itoh K. Serum amyloid A1 alleles and plasma concentrations of serum amyloid A. Amyloid. 1999;6:199–204.

    PubMed  Article  CAS  Google Scholar 

  21. Soh D, Dong D, Guo Y, Wong L. Consistency, comprehensiveness, and compatibility of pathway databases. BMC Bioinform. 2010;11:449.

    Article  Google Scholar 

  22. Kanehisa M. Representation and analysis of molecular networks involving diseases and drugs. Genome Inform. 2009;23:212–3.

    PubMed  Article  Google Scholar 

  23. Kelder T, Pico AR, Hanspers K, van Iersel MP, Evelo C, Conklin BR. Mining biological pathways using WikiPathways web services. PLoS One. 2009;4:e6447.

    PubMed  Article  Google Scholar 

  24. Pico AR, Kelder T, van Iersel MP, Hanspers K, Conklin BR, Evelo C. WikiPathways: pathway editing for the people. PLoS Biol. 2008;6:e184.

    PubMed  Article  Google Scholar 

  25. Jimenez-Marin A, Collado-Romero M, Ramirez-Boo M, Arce C, Garrido JJ. Biological pathway analysis by ArrayUnlock and ingenuity pathway analysis. BMC Proc 2009;3 Suppl 4:S6.

    Google Scholar 

  26. Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res. 2000;2:189–202.

    PubMed  Article  CAS  Google Scholar 

  27. Lappalainen T, Kolehmainen M, Schwab U, Pulkkinen L, Laaksonen DE, Rauramaa R, et al. Serum concentrations and expressions of serum amyloid A and leptin in adipose tissue are interrelated: the Genobin Study. Eur J Endocrinol. 2008;158:333–41.

    PubMed  Article  CAS  Google Scholar 

  28. Chen X, Zhang H, McAfee S, Zhang C. The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice. Am J Physiol Heart Circ Physiol. 2010;299:H605–12.

    PubMed  Article  CAS  Google Scholar 

  29. Huebener P, Abou-Khamis T, Zymek P, Bujak M, Ying X, Chatila K, et al. CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol. 2008;180:2625–33.

    PubMed  CAS  Google Scholar 

  30. Lutgens E, Lievens D, Beckers L, Wijnands E, Soehnlein O, Zernecke A, et al. Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile. J Exp Med. 2010;207:391–404.

    PubMed  Article  CAS  Google Scholar 

  31. Cantor J, Haskins K. Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: evidence for involvement of CCR8 and CCL1. J Immunol. 2007;179:5760–7.

    PubMed  CAS  Google Scholar 

  32. Cheung R, Malik M, Ravyn V, Tomkowicz B, Ptasznik A, Collman RG. An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages. J Leukoc Biol. 2009;86:833–45.

    PubMed  Article  CAS  Google Scholar 

  33. Sokolov VO, Krasnikova TL, Prokofieva LV, Kukhtina NB, Arefieva TI. Expression of markers of regulatory CD4+CD25+foxp3+ cells in atherosclerotic plaques of human coronary arteries. Bull Exp Biol Med. 2009;147:726–9.

    PubMed  Article  CAS  Google Scholar 

  34. Lee JG, Lim EJ, Park DW, Lee SH, Kim JR, Baek SH. A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation. Cell Signal. 2008;20:2266–75.

    PubMed  Article  CAS  Google Scholar 

  35. Zhao L, Lee E, Zukas AM, Middleton MK, Kinder M, Acharya PS, et al. CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2008;28:1283–9.

    PubMed  Article  CAS  Google Scholar 

  36. Hagg D, Sjoberg S, Hulten LM, Fagerberg B, Wiklund O, Rosengren A, et al. Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop? Atherosclerosis. 2007;190:291–7.

    PubMed  Article  Google Scholar 

  37. Zhao L, Hall JA, Levenkova N, Lee E, Middleton MK, Zukas AM, et al. CD44 regulates vascular gene expression in a proatherogenic environment. Arterioscler Thromb Vasc Biol. 2007;27:886–92.

    PubMed  Article  CAS  Google Scholar 

  38. Stonik JA, Remaley AT, Demosky SJ, Neufeld EB, Bocharov A, Brewer HB. Serum amyloid A promotes ABCA1-dependent and ABCA1-independent lipid efflux from cells. Biochem Biophys Res Commun. 2004;321:936–41.

    PubMed  Article  CAS  Google Scholar 

  39. Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring). 2010;18:884–9.

    Article  CAS  Google Scholar 

  40. Poitou C, Viguerie N, Cancello R, De Matteis R, Cinti S, Stich V, et al. Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition. Diabetologia. 2005;48:519–28.

    PubMed  Article  CAS  Google Scholar 

  41. Ishikawa Y, Akasaka Y, Ito K, Akishima Y, Kimura M, Kiguchi H, et al. Significance of anatomical properties of myocardial bridge on atherosclerosis evolution in the left anterior descending coronary artery. Atherosclerosis. 2006;186:380–9.

    PubMed  Article  CAS  Google Scholar 

  42. Ishikawa Y, Akasaka Y, Suzuki K, Fujiwara M, Ogawa T, Yamazaki K, et al. Anatomic properties of myocardial bridge predisposing to myocardial infarction. Circulation. 2009;120:376–83.

    PubMed  Article  Google Scholar 

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Acknowledgments

We would like to express our appreciation to Prof. Wong Limsoon for the valuable advice offered during the course of this project. This work was generously supported by the National Medical Research Council, Singapore (Grant NMRC/1155/2008). K.-Y. Leow is supported by a National University of Singapore research scholarship.

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Affiliations

  1. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 1E, Kent Ridge Road, Singapore, 119228, Singapore

    Koon-Yeow Leow & Chew-Kiat Heng

  2. Department of Computing, Imperial College London, London, UK

    Wilson Wen Bin Goh

  3. School of Computing, National University of Singapore, 21 Lower Kent Ridge Rd, Singapore, 119077, Singapore

    Wilson Wen Bin Goh

Authors
  1. Koon-Yeow Leow
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  2. Wilson Wen Bin Goh
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  3. Chew-Kiat Heng
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Corresponding author

Correspondence to Chew-Kiat Heng.

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Responsible Editor: Graham Wallace.

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Leow, KY., Goh, W.W.B. & Heng, CK. Effect of serum amyloid A1 treatment on global gene expression in THP-1-derived macrophages. Inflamm. Res. 61, 391–398 (2012). https://doi.org/10.1007/s00011-011-0424-4

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  • DOI: https://doi.org/10.1007/s00011-011-0424-4

Keywords

  • Serum amyloid A1
  • Atherosclerosis
  • Acute-phase protein
  • Coronary artery disease
  • Rheumatoid arthritis