Journal of Molecular Histology

, Volume 41, Issue 6, pp 379–386 | Cite as

Tissue distribution and expression of paraoxonases and chemokines in mouse: the ubiquitous and joint localisation suggest a systemic and coordinated role

  • Fernando Rodríguez-Sanabria
  • Anna Rull
  • Raúl Beltrán-Debón
  • Gerard Aragonès
  • Jordi Camps
  • Bharti Mackness
  • Michael Mackness
  • Jorge Joven
Original Paper

Abstract

A vicious cycle between oxidation and inflammation leads to complications in a growing number of disease states. Knowledge on tissue distribution of chemokines, mediators of inflammatory response, and paraoxonases, with antioxidant and anti-inflammatory actions, may be relevant. Using immunohistochemistry and quantitative real-time PCR we have investigated the distribution of PON1, 2 and 3, CCL2, 7, 8 and 12 and the chemokine receptor CCR2 protein and mRNA in 23 tissues from C57BL/6J mice. As expected, PON1, 2 and 3, CCL2, 7, 8 and 12 and CCR2 proteins were present in the vast majority of tissues investigated. Surprisingly, mRNA for these proteins was also expressed in most of these tissues suggesting local production and the ability to respond in situ to inflammatory stimuli. The wide distribution and expression of mRNA for paraoxonases and CC-chemokines suggest a systemic, probably coordinated, role in the overall inflammatory response.

Keywords

CCR2 Chemokines Inflammation Monocyte-chemoattractant protein Paraoxonase 

Notes

Acknowledgments

Supported by grants from the Instituto de Salud Carlos III (PI081175 and PI081381), Ministerio de Sanidad, Madrid, Spain. GA, AR, and RBD are recipients of post-graduate fellowships from the Generalitat de Catalunya (FI06/01054, SGR00503, and FI08/00064 respectively). FRS is a visiting scientist from the Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. Expert technical assistance was provided by Alba Folch and Núria Canela.

Supplementary material

10735_2010_9299_MOESM1_ESM.doc (26 kb)
Supplementary material 1 (DOC 25 kb)
10735_2010_9299_MOESM2_ESM.doc (46 kb)
Supplementary material 2 (DOC 45 kb)

References

  1. Aviram M, Rosenblat M (2004) Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37:1304–1316CrossRefPubMedGoogle Scholar
  2. Azfer A, Niu J, Rogers LM, Adamski FM, Kolattukudy PE (2006) Activation of endoplasmic reticulum stress response during the development of ischemic heart disease. Am J Physiol Heart Circ Physiol 291:H1411–H1420CrossRefPubMedGoogle Scholar
  3. Boring L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897CrossRefPubMedGoogle Scholar
  4. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621CrossRefPubMedGoogle Scholar
  5. Dewald O, Zymek P, Winkelmann K, Koerting A, Ren G, Abou-Khamis T, Michael LH, Rollins BJ, Entman ML, Frangogiannis NG (2005) CCL2/Monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ Res 96:881–889CrossRefPubMedGoogle Scholar
  6. Draganov DI, La Du BN (2004) Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol 369:78–88CrossRefPubMedGoogle Scholar
  7. Han KH, Tangirala RK, Green SR, Quehenberger O (1998) Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma LDL. Arterioscler Thromb Vasc Biol 18:1983–1991PubMedGoogle Scholar
  8. Mackness B, Mackness M (2010) Anti-inflammatory properties of paraoxonase-1 in atherosclerosis. Adv Exp Med Biol 660:143–151CrossRefPubMedGoogle Scholar
  9. Mackness B, Hine D, Liu Y, Mastorikou M, Mackness M (2004) Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells. Biochem Biophys Res Commun 318:680–683CrossRefPubMedGoogle Scholar
  10. Mackness B, Beltran-Debon R, Aragones G, Joven J, Camps J, Mackness M (2010) Human tissue distribution of paraoxonases 1 and 2 mRNA. IUBMB Life 62:480–482PubMedGoogle Scholar
  11. Marsillach J, Mackness B, Mackness M, Riu F, Beltran R, Joven J, Camps J (2008) Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues. Free Radic Biol Med 45:146–157CrossRefPubMedGoogle Scholar
  12. Mastorikou M, Mackness B, Liu Y, Mackness M (2008) Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high-density lipoprotein to metabolize membrane lipid hydroperoxides. Diabet Med 25:1049–1055CrossRefPubMedGoogle Scholar
  13. Ng CJ, Wadleigh DJ, Gangopadhyay A, Hama S, Grijalva VR, Navab M, Fogelman AM, Reddy ST (2001) Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276:44444–44449CrossRefPubMedGoogle Scholar
  14. Ng CJ, Bourquard N, Hama SY, Shih D, Grijalva VR, Navab M, Fogelman AM, Reddy ST (2007) Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27:1368–1374CrossRefPubMedGoogle Scholar
  15. Niu J, Kolattukudy PE (2009) Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Sci (Lond) 117:95–109CrossRefGoogle Scholar
  16. Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN (1996) The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 33:498–507CrossRefPubMedGoogle Scholar
  17. Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM (2001) Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21:542–547PubMedGoogle Scholar
  18. Reddy ST, Devarajan A, Bourquard N, Shih D, Fogelman AM (2008) Is it just paraoxonase 1 or are other members of the paraoxonase gene family implicated in atherosclerosis? Curr Opin Lipidol 19:405–408CrossRefPubMedGoogle Scholar
  19. Roca H, Varsos ZS, Mizutani K, Pienta KJ (2008) CCL2, survivin and autophagy: new links with implications in human cancer. Autophagy 4:969–971PubMedGoogle Scholar
  20. Rong JX, Berman JW, Taubman MB, Fisher EA (2002) Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol 22:1617–1623CrossRefPubMedGoogle Scholar
  21. Rull A, Beltran-Debon R, Aragones G, Rodriguez-Sanabria F, Alonso-Villaverde C, Camps J, Joven J (2010a) Expression of cytokine genes in the aorta is altered by the deficiency in MCP-1: effect of a high-fat, high-cholesterol diet. Cytokine 50:121–128CrossRefPubMedGoogle Scholar
  22. Rull A, Camps J, Alonso-Villaverde C, Joven J (2010b) Insulin resistance and inflammation: is monocyte chemoattractant protein-1 (MCP-1/CCL2) a relevant effector in the regulation of metabolism? Mediators of inflammation (in press)Google Scholar
  23. Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ (2000) Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 96:34–40PubMedGoogle Scholar
  24. Sears DD, Miles PD, Chapman J, Ofrecio JM, Almazan F, Thapar D, Miller YI (2009) 12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice. PLoS One 4:e7250CrossRefPubMedGoogle Scholar
  25. Shih DM, Xia YR, Yu JM, Lusis AJ (2010) Temporal and tissue-specific patterns of Pon3 expression in mouse: In situ hybridization analysis. Adv Exp Med Biol 660:73–87CrossRefPubMedGoogle Scholar
  26. Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A 81:3883–3887CrossRefPubMedGoogle Scholar
  27. Younce CW, Kolattukudy PE (2010) MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel zinc-finger protein, MCPIP. Biochem J 426:43–53CrossRefPubMedGoogle Scholar
  28. Zhou L, Azfer A, Niu J, Graham S, Choudhury M, Adamski FM, Younce C, Binkley PF, Kolattukudy PE (2006) Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ Res 98:1177–1185CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Fernando Rodríguez-Sanabria
    • 1
  • Anna Rull
    • 1
  • Raúl Beltrán-Debón
    • 1
  • Gerard Aragonès
    • 1
  • Jordi Camps
    • 1
  • Bharti Mackness
    • 1
  • Michael Mackness
    • 1
  • Jorge Joven
    • 1
  1. 1.Centre de Recerca Biomèdica. Hospital Universitari de Sant Joan. Institut d´Investigació Sanitària Pere Virgili (IISPV)Universitat Rovira i VirgiliReusSpain

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