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Cited by 17Adenosine and Purinergic SignalingWound Healing and TreatmentsImmune Response and Inflammation

Anti Inflammatory Property of PDRN—An in Vitro Study on Cultured Macrophages

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Castellini, Chiara, Belletti, Silvana, Govoni, Paolo, Guizzardi, Stefano·2017·Advances in Bioscience and Biotechnology
DOI 10.4236/abb.2017.81002
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Abstract

Skin aging and most age-related diseases are associated with a low-grade chronic inflammation. The nucleoside adenosine, a potent endogenous anti-inflammatory agent, is deeply involved in inflammatory diseases and, by interaction with the adenosine A2 receptor (A2AR) it immediately promotes a mechanism of defence against the inflammatory damage. The aim of our study was to investigate whether polydeoxyribonucleotide (PDRN), a mixture of deoxyribonucleotides polymers of different lengths that like adenosine, binds the A2A receptor, can reduce the inflammatory state in the macrophage cell line. RAW264.7, murine macrophage cells, were incubated with PDRN in the presence and in the absence of lipopolysaccaride (LPS), which was the major component of the outer membrane of gram-negative bacteria and which acted as a strong macrophage activator. We assessed the production of nitric oxide and the secretion of inflammatory mediators (i.e., TNF-α, IL-10, IL-12 and VEGF-A). Our data showed that PDRN produced a significant decrease of inflammation in macrophages pre-stimulated with LPS, assessed in terms of the nitric oxide content (p 2A receptor, contributed to a great extent towards reducing inflammation.

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Research works printed but not linked: 37

  1. Singh, T. and Newman, A.B. (2011) Inflammatory Markers in Population Studies of Aging. Ageing Research Reviews, 10, 319-329. https://doi.org/10.1016/j.arr.2010.11.002 · DOI
  2. Chung, H.Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A.Y., et al. (2009) Molecular Inflammation: Underpinnings of Aging and Age-Related Dis- eases. Ageing Research Reviews, 8, 18-30. https://doi.org/10.1016/j.arr.2008.07.002 · DOI · Paper page
  3. Franceschi, C., Bonafe, M., Valensin, S., Olivieri, F., De Luca, M., Ottaviani, E., et al. (2000) Inflamm-Aging: An Evolutionary Perspective on Immunosenescence. An- nals of the New York Academy of Sciences, 908, 244-254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x · DOI · Paper page
  4. Zhuang, Y. and Lyga, J. (2014) Inflammaging in Skin and Other Tissues-The Roles of Complement System and Macrophage. Inflammation & Allergy-Drug Targets, 13, 153-161. https://doi.org/10.2174/1871528113666140522112003 · DOI
  5. Makrantonaki, E. and Zouboulis, C.C. (2007) Molecular Mechanisms of Skin Aging: State of the Art. Annals of the New York Academy of Sciences, 1119, 40-50. https://doi.org/10.1196/annals.1404.027 · DOI
  6. Plowden, J., Renshaw-Hoelscher, M., Engleman, C., Katz, J. and Sambhara, S. (2004) Innate Immunity in Aging: Impact on Macrophage Function. Aging Cell, 3, 161-167. https://doi.org/10.1111/j.1474-9728.2004.00102.x · DOI
  7. Shaw, A.C., Joshi, S., Greenwood, H., Panda, A. and Lord, J.M. (2010) Aging of the Innate Immune System. Current Opinion in Immunology, 22, 507-513. https://doi.org/10.1016/j.coi.2010.05.003 · DOI · Paper page
  8. Baylis, D., Bartlett, D.B., Patel, H.P. and Roberts, H.C. (2013) Understanding How We Age: Insights into Inflammaging. Longevity & Healthspan, 2, 8. https://doi.org/10.1186/2046-2395-2-8 · DOI
  9. Gay, N.J. and Gangloff, M. (2007) Structure and Function of Toll Receptors and Their Ligands. Annual Reviews Biochemistry, 76, 141-165. https://doi.org/10.1146/annurev.biochem.76.060305.151318 · DOI
  10. Gangloff, M. (2012) Different Dimerisation Mode for TLR4 upon Endosomal Acidi- fication? Trends in Biochemical Sciences, 37, 92-98. https://doi.org/10.1016/j.tibs.2011.11.003 · DOI
  11. Cannizzo, E.S., Clement, C.C., Sahu, R., Follo, C. and Santambrogio, L. (2011) Oxi- dative Stress, Inflamm-Aging and Immunosenescence. Journal of Proteomics, 74, 2313-2323. https://doi.org/10.1016/j.jprot.2011.06.005 · DOI
  12. Martinez, F.O., Sica, A., Mantovani, A. and Locati, M. (2008) Macrophage Activa- tion and Polarization. Frontiers in Bioscience, 13, 453-461. https://doi.org/10.2741/2692 · DOI · Paper page
  13. Ferrante, C.J. and Leibovich, S.J. (2011) Regulation of Macrophage Polarization and Wound Healing. Advances in Wound Care, 1, 10-16. https://doi.org/10.1089/wound.2011.0307 · DOI
  14. Grinberg, S., Hasko, G., Wu, D. and Leibovich, S.J. (2009) Suppression of PLCβ2 by Endotoxin Plays a Role in the Adenosine A 2A Receptor-Mediated Switch of Macro- phages from an Inflammatory to an Angiogenic Phenotype. American Journal of Pathology, 175, 2439-2453. https://doi.org/10.2353/ajpath.2009.090290 · DOI
  15. Palmer, T.M. and Trevethick, M.A. (2008) Suppression of Inflammatory and Im- mune Responses by the A 2A Adenosine Receptor: An Introduction. British Journal of Pharmacology, 153, S27-S34. https://doi.org/10.1038/sj.bjp.0707524 · DOI
  16. Cohen, S.B., Leo, B.M., Baer, G.S., Turner, M.A., Beck, G. and Diduch, D.R. (2005) An Adenosine A 2A Receptor Agonist Reduces Interleukin-8 Expression and Glyco- saminoglycan Loss Following Septic Arthrosis. Journal of Orthopaedic Research, 23, 1172-1178. https://doi.org/10.1016/j.orthres.2005.01.015 · DOI
  17. Campo, G.M., Avenoso, A., D'Ascola, A., Prestipino, V., Scuruchi, M., Nastasi, G., et al. (2012) Hyaluronan Differently Modulates TLR-4 and the Inflammatory Re- sponse in Mouse Chondrocytes. Biofactors, 38, 69-76. https://doi.org/10.1002/biof.202 · DOI
  18. Valdatta, L., Thione, A., Mortarino, C., Buoro, M. and Tuinder, S. (2004) Evalua- tion of the Efficacy of Polydeoxyribonucleotides in the Healing Process of Autolo- gous Skin Graft Donor Sites: A Pilot Study. Current Medical Research and Opinion, 20, 403-408. https://doi.org/10.1185/030079904125003116 · DOI · Paper page
  19. Tonello, G., Daglio, M., Zaccarelli, N., Sottofattori, E., Mazzei, M. and Balbi, A. (1996) Characterization and Quantitation of the Active Polynucleotide Fraction (PDRN) from Human Placenta, a Tissue Repair Stimulating Agent. Journal of Phar- maceutical and Biomedical Analysis, 14, 1555-1560. https://doi.org/10.1016/0731-7085(96)01788-8 · DOI · Paper page
  20. O'Brien, J., Wilson, I., Orton, T. and Pognan, F. (2000) Investigation of the Alamar Blue (Resazurin) Fluorescent Dye for the Assessment of Mammalian Cell Cytotoxi- city. European Journal of Biochemistry, 267, 5421-5426. https://doi.org/10.1046/j.1432-1327.2000.01606.x · DOI · Paper page
  21. Misko, T.P., Schilling, R.J., Salvemini, D., Moore, W.M. and Currie, M.G. (1993) A Fluorometric Assay for the Measurement of Nitrite in Biological Samples. Analyti- cal Biochemistry, 214, 11-16. https://doi.org/10.1006/abio.1993.1449 · DOI
  22. De la Fuente, M. and Miquel, J. (2009) An Update of the Oxidation-Inflammation Theory of Aging: The Involvement of the Immune System in Oxi-Inflamm-Aging. Current Pharmaceutical Design, 15, 3003-3026. https://doi.org/10.2174/138161209789058110 · DOI · Paper page
  23. Bennett, M.F., Robinson, M.K., Baron, E.D. and Cooper, K.D. (2008) Skin Immune Systems and Inflammation: Protector of the Skin or Promoter of Aging? Journal of Investigative Dermatology Symposium Proceedings, 13, 15-19. https://doi.org/10.1038/jidsymp.2008.3 · DOI
  24. Eppell, B.A., Newell, A.M. and Brown, E.J. (1989) Adenosine Receptors Are Ex- pressed during Differentiation of Monocytes to Macrophages in Vitro: Implications for Regulation of Phagocytosis. Journal of Immunology, 143, 4141-4145.
  25. Fredholm, B.B., Chern, Y., Franco, R. and Sitkovsky, M. (2007) Aspects of the Gen- eral Biology of Adenosine A 2A Signaling. Progress in Neurobiology, 83, 263-276. https://doi.org/10.1016/j.pneurobio.2007.07.005 · DOI
  26. Hasko, G., Kuhel, D.G., Chen, J.F., Schwarzschild, M.A., Deitch, E.A., Mabley, J.G., et al. (2000) Adenosine Inhibits IL-12 and TNF-[Alpha] Production via Adenosine A 2a Receptor-Dependent and Independent Mechanisms. The FASEB Journal, 14, 2065-2074. https://doi.org/10.1096/fj.99-0508com · DOI
  27. Varani, K., Vincenzi, F., Tosi, A., Targa, M., Masieri, F.F., Ongaro, A., et al. (2010) Expression and Functional Role of Adenosine Receptors in Regulating Inflamma- tory Responses in Human Synoviocytes. British Journal of Pharmacology, 160, 101- 115. https://doi.org/10.1111/j.1476-5381.2010.00667.x · DOI
  28. Bitto, A., Oteri, G., Pisano, M., Polito, F., Irrera, N., Minutoli, L., et al. (2013) Ade- nosine Receptor Stimulation by Polynucleotides (PDRN) Reduces Inflammation in Experimental Periodontitis. Journal of Clinical Periodontology, 40, 26-32. https://doi.org/10.1111/jcpe.12010 · DOI
  29. Bitto, A., Polito, F., Irrera, N., D'Ascola, A., Avenoso, A., Nastasi, G., et al. (2011) Polydeoxyribonucleotide Reduces Cytokine Production and the Severity of Colla- gen-Induced Arthritis by Stimulation of Adenosine A 2A Receptor. Arthritis & Rheu- matology, 63, 3364-3371. https://doi.org/10.1002/art.30538 · DOI · Paper page
  30. Montesinos, M.C., Gadangi, P., Longaker, M., Sung, J., Levine, J., Nilsen, D., et al. (1997) Wound Healing Is Accelerated by Agonists of Adenosine A2 (G Alpha S- Linked) Receptors. The Journal of Experimental Medicine, 186, 1615-1620.
  31. Fischer, S., Knoll, R., Renz, D., Karliczek, G.F. and Schaper, W. (1997) Role of Ade- nosine in the Hypoxic Induction of Vascular Endothelial Growth Factor in Porcine Brain Derived Microvascular Endothelial Cells. Journal of Endothelial Cell Re- search, 5, 155-165. https://doi.org/10.3109/10623329709053395 · DOI
  32. Gu, J.W., Brady, A.L., Anand, V., Moore, M.C., Kelly, W.C. and Adair, T.H. (1999) Adenosine Up-Regulates VEGF Expression in Cultured Myocardial Vascular Smooth Muscle Cells. American Journal of Physiology, 277, H595-H602.
  33. Leibovich, S.J., Chen, J.F., Pinhal-Enfield, G., Belem, P.C., Elson, G., Rosania, A., et al. (2002) Synergistic Up-Regulation of Vascular Endothelial Growth Factor Expre- ssion in Murine Macrophages by Adenosine A 2A Receptor Agonists and Endotoxin. American Journal of Physiology, 160, 2231-2244. https://doi.org/10.1016/S0002-9440(10)61170-4 · DOI
  34. Hasko, G. and Cronstein, B.N. (2004) Adenosine: An Endogenous Regulator of In- nate Immunity. Trends in Immunology, 25, 33-39. https://doi.org/10.1016/j.it.2003.11.003 · DOI
  35. Linden, J. (2005) Adenosine in Tissue Protection and Tissue Regeneration. Mole- cular Pharmacology, 67, 1385-1387. https://doi.org/10.1124/mol.105.011783 · DOI
  36. Polito, F., Bitto, A., Galeano, M., Irrera, N., Marini, H., Calo, M., et al. (2012) Poly- deoxyribonucleotide Restores Blood Flow in an Experimental Model of Ischemic Skin Flaps. Journal of Vascular Surgery, 55, 479-488. https://doi.org/10.1016/j.jvs.2011.07.083 · DOI
  37. Squadrito, F., Bitto, A., Altavilla, D., Arcoraci, V., De Caridi, G., De Feo, M.E., et al. (2014) The Effect of PDRN, an Adenosine Receptor A 2A Agonist, on the Healing of Chronic Diabetic Foot Ulcers: Results of a Clinical Trial. The Journal of Clinical Endocrinology & Metabolism, 99, E746-E753. https://doi.org/10.1210/jc.2013-3569 Submit or recommend next manuscript to SCIRP and we will provide best service for you: Accepting pre-submission inquiries through Email, Facebook, LinkedIn, Twitter, etc. A wide selection of journals (inclusive of 9 subjects, more than 200 journals) Providing 24-hour high-quality service User-friendly online submission system Fair and swift peer-review system Efficient typesetting and proofreading procedure Display of the result of downloads and visits, as well as the number of cited articles Maximum dissemination of your research work Submit your manuscript at: http://papersubmission.scirp.org/ Or contact abb@scirp.org · DOI

Cited by

Sorted by citations

Authors
Castellini, C., Belletti, S., Govoni, P., & Guizzardi, S.
Affiliations
University of Parma (IT)
ORCID
Venue
Advances in Bioscience and Biotechnology
Publisher
Scientific Research Publishing, Inc.
Published
2017
Volume
08
Issue
01
Pages
13-26
ISSN
  • 2152-7296 (ISSN-L)
  • 2156-8456
  • 2156-8502
DOI
10.4236/abb.2017.81002
OpenAlex
W2572877214
Cited by
17
References
3
Citations by year
2026: 1 · 2025: 7 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 2
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
Advances in Bioscience and Biotechnology (publishedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
polydeoxyribonucleotide, adenosine A2A receptor, anti-inflammatory activity, macrophages, RAW 264.7 macrophages, lipopolysaccharide, nitric oxide, TNF-α, IL-10, IL-12, VEGF-A, skin aging, chronic inflammation

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