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Expression and Secretion of RANTES (CCL5) in Granulomatous Calcified Tissue before and after Lipopolysaccharide Treatment In Vivo

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Abstract

RANTES (regulated on activation, normal T cell-expressed and secreted) is a CC chemokine appearing to be involved in the recruitment of leukocytes at inflammation sites. RANTES is produced by CD8+ T cells, epithelial cells, fibroblasts, and platelets. It acts in vitro in leukocyte activation and human immunodeficiency virus suppression, but its role in vivo is still uncertain. In our study, we established the involvement of RANTES in an in vivo model of chronic inflammation induced by potassium permanganate, leading to calcified granulomas. In our rat model, RANTES expression (mRNA and protein) was significantly upregulated in granulomatous tissue; RANTES expression was further increased upon i.p. injection of lipopolysaccharide (LPS), while it was kept at basal levels by dexamethasone (Dex) given 18 hours before sacrifice. LPS and Dex increased and decreased, respectively, the recruitment of mononuclear cells in granulomatous tissue compared with control granulomas from phosphate-buffered saline (PBS)-treated animals. In granuloma tissue, levels of RANTES were higher in LPS-treated rats and lower in the Dex group compared to controls. RANTES was also found in the conditioned medium of granuloma tissue from treated (LPS or Dex) and untreated (PBS) rats. When LPS was added in vitro for 18 hours, RANTES was further increased, except in the Dex group (P > 0.05). On serum analysis, RANTES levels were higher in the LPS group and lower in the Dex group compared to controls. This study shows for the first time that RANTES is produced in vivo in chronic, experimental inflammatory states, an effect increased by LPS and inhibited by Dex.

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References

  1. Conti P, Barbacane RC, Reale M (1999) Chemokines in inflammatory states. Allergy Asthma Proc 20:205–208

    Article  PubMed  CAS  Google Scholar 

  2. Conti P, DiGioacchino M (2001) MCP-1 and RANTES are mediators of acute and chronic inflammation. Allergy Asthma Proc 22:133–137

    Article  PubMed  CAS  Google Scholar 

  3. Matalon R, Surendran S, McDonald JD, Okorodudu AO, Tyring SK, Michals-Matalon K, Harris P (2005) Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring. Int J Immunopathol Pharmacol 18:557–565

    PubMed  CAS  Google Scholar 

  4. Gorbunov NV, McFaul SJ, Januszkiewicz A, Atkins JL (2005) Pro-inflammatory alterations and status of blood plasma iron in a model of blast-induced lung trauma. Int J Immunopathol Pharmacol 18:547–556

    PubMed  CAS  Google Scholar 

  5. Frydas S, Papaioannou N, Papazahariadou M, Hatzistilianou M, Karagouni E, Trakatelli M, Brellou G, Petrarca C, Castellani ML, Conti P, Riccioni G, Patruno A, Grilli A (2005) Inhibition of MCP-1 and MIP-2 chemokines in murine trichinellosis: effect of the anti-inflammatory compound L-mimosine. Int J Immunopathol Pharmacol 18:85–94

    PubMed  CAS  Google Scholar 

  6. Musso T, Cappello P, Stornello S, Ravarino D, Caorsi C, Otero K, Novelli F, Badolato R, Giovarelli M (2005) IL-10 enhances CCL2 release and chemotaxis induced by CCL16 in human monocytes. Int J Immunopathol Pharmacol 18:339–349

    PubMed  CAS  Google Scholar 

  7. Di Giannantonio M, Frydas S, Kempuraj D, Karagouni E, Hatzistilianou M, Conti CM, Boucher W, Papadopoulou N, Donelan J, Cao J, Madhappan B, Boscolo P, Petrarca C, Castellani L, Quartesan L, Doyle R, Ferro FM (2005) Cytokines in stress. Int J Immunopathol Pharmacol 18:1–5

    PubMed  CAS  Google Scholar 

  8. Conti P, Pang X, Boucher W, Letourneau R, Reale M, Barbacane RC, Thibault J, Theoharides TC (1997) RANTES is a pro-inflammatory chemokine and chemoattracts basophil cells to extravascular sites. J Pathol 183:352–358

    Article  PubMed  CAS  Google Scholar 

  9. Conti P, Reale M, Barbacane RC, Felaco M, Grilli A, Theoharides TC (1998) Mast cell recruitment after subcutaneous injection of RANTES in the sole of the rat paw. Br J Haematol 103:798–803

    Article  PubMed  CAS  Google Scholar 

  10. Petrarca C, Frydas S, Donelan J, Boucher W, Papadopoulou N, Cao J, Castellani ML, Conti P, Toniato E, Robuffo I, Vecchiet J, Iezzi T, Madhappan B, Kempuraj D (2005) Interleukin 27 (IL-27): a novel pleiotropic cytokine involved in T cell differentiation and T cell response modulation. Int J Immunopathol Pharmacol 18:191–194

    PubMed  CAS  Google Scholar 

  11. Cavalieri B, Mosca M, Ramadori P, Perrelli MG, De Simone L, Colotta F, Bestini R, Poli G, Cutrin JC (2005) Neutrophil recruitment in the reperfused-injured rat liver was effectively attenuated by repertaxin, a novel allosteric noncompetitive inhibitor of CXCL8 receptors: a therapeutic approach for the treatment of post-ischemic hepatic syndromes. Int J Immunopathol Pharmacol 18:475–486

    PubMed  CAS  Google Scholar 

  12. Cianci R, Pinti M, Nasi M, Starnino S, Cammarota G, Miele L, De Luca A, Cauda R, Raducci F, Grieco A, Rapaccini G, Gasbarrini G, Cossarizza A, Pandolfi F (2005) Impairment of recent thymic emigrants in HCV infection. Int J Immunopathol Pharmacol 18:723–728

    PubMed  CAS  Google Scholar 

  13. Luther SA, Cyster JG (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2:102–107

    Article  PubMed  CAS  Google Scholar 

  14. Gioia C, Horejsh D, Agrati C, Martini F, Capobianchi MR, Ippolito G, Poccia F (2005) T-cell response profiling to biological threat agents including the SARS coronavirus. Int J Immunopathol Pharmacol 18:525–530

    PubMed  CAS  Google Scholar 

  15. Cipollone F, Chiarelli F, Iezzi A, Fazia ML, Cuccurullo C, Pini B, De Cesare D, Torello M, Tumini S, Cuccurullo F, Mezzetti A (2005) Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes. Int J Immunopathol Pharmacol 18:625–635

    PubMed  CAS  Google Scholar 

  16. Gonzalez MI, Rubinstein N, Ilarregui JM, Toscano MA, Sanjuan NA, Rabinovich GA (2005) Regulated expression of galectin-1 after in vitro productive infection with herpes simplex virus type 1: implications for T cell apoptosis. Int J Immunopathol Pharmacol 18:615–623

    PubMed  CAS  Google Scholar 

  17. Appay V, Rowland-Jones SL (2001) RANTES: a versatile and controversial chemokine. Trends Immunol 22:83–87

    Article  PubMed  CAS  Google Scholar 

  18. De Luca M, Miccinesi G, Chiappini E, Zappa M, Galli L, De Martino M (2005) Different kinetics of immunologic recovery using nelfinavir or lopinavir/ritonavir-based regimens in children with perinatal HIV-1 infection. Int J Immunopathol Pharmacol 18:729–735

    PubMed  Google Scholar 

  19. Martini F, Agrati C, D’Offizi G, Poccia F (2005) HLA-E up-regulation induced by HIV infection may directly contribute to CD94-mediated impairment of NK cells. Int J Immunopathol Pharmacol 18:269–276

    PubMed  CAS  Google Scholar 

  20. Conti P, Pang X, Boucher W, Letourneau R, Reale M, Barbacane RC, Thibault J, Theoharides TC (1997) Impact of RANTES and MCP-1 chemokines on in vivo basophilic cell recruitment in rat skin injection model and their role in modifying the protein and mRNA levels for histidine decarboxylase. Blood 89:4120–4127

    PubMed  CAS  Google Scholar 

  21. Conti P, Reale M, Barbacane RC, Letourneau R, Theoharides TC (1998) Intramuscular injection of hrRANTES causes mast cell recruitment and increased transcription of histidine decarboxylase in mice: lack of effects in genetically mast cell-deficient W/WV mice. FASEB J 12:1693–1700

    PubMed  CAS  Google Scholar 

  22. Ballerini P, Di Iorio P, Ciccarelli R, Caciagli F, Poli A, Beraudi A, Buccella S, D’Alimonte I, D’Auro M, Nargi E, Patricelli P, Visini D, Traversa U (2005) P2Y1 and cysteinyl leukotriene receptors mediate purine and cysteinyl leukotriene co-release in primary cultures of rat microglia. Int J Immunopathol Pharmacol 18:255–268

    PubMed  CAS  Google Scholar 

  23. Ballerini P, Ciccarelli R, Caciagli F, Rathbone MP, Werstiuk ES, Traversa U, Buccella S, Giuliani P, Jang S, Nargi E, Visini D, Santavenere C, Di Iorio P (2005) P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes. Int J Immunopathol Pharmacol 18:417–430

    PubMed  CAS  Google Scholar 

  24. Weber C, Kitayama J, Springer TA (1996) Differential regulation of ß1 and ß2 integrin avidity by chemoattractants in eosinophils. Proc Natl Acad Sci USA 93:10939–10944

    Article  PubMed  CAS  Google Scholar 

  25. Di Lorenzo G, Pacor ML, Mansueto P, Esposito Pellitteri M, Lo Bianco C, Ditta V, Leto-Barone MS, Napoli N, Di Fede G, Rini GB (2005) Determinants of bronchial hyperresponsiveness in subjects with rhinitis. Int J Immunopathol Pharmacol 18:715–722

    PubMed  CAS  Google Scholar 

  26. Bernardini R, Mistrello G, Novembre E, Roncarolo D, Zanotta S, Lombardi E, Cianferoni A, Pucci N, De Martino M, Vierucci A (2005) Cross-reactivity between IgE-binding proteins from Anisakis simplex and Dermatophagoides pteronyssinus. Int J Immunopathol Pharmacol 18:671–675

    PubMed  CAS  Google Scholar 

  27. Liu Q, Hamblin MR (2005) Macrophage-targeted photodynamic therapy: scavenger receptor expression and activation state. Int J Immunopathol Pharmacol 18:391–402

    PubMed  CAS  Google Scholar 

  28. Appay V, Rowland-Jones SL (2001) RANTES: a versatile and controversial chemokine. Trends Immunol 22:83–87

    Article  PubMed  CAS  Google Scholar 

  29. Marinova S, Nenkov P, Markova R, Nikolaeva S, Kostadinova R, Mitov I, Vretenarska M (2005) Cellular and humoral systemic and mucosal immune responses stimulated by an oral polybacterial immunomodulator in patients with chronic urinary tract infections. Int J Immunopathol Pharmacol 18:457–473

    PubMed  CAS  Google Scholar 

  30. Ottonello L, Bertolotto M, Montecucco F, Dapino P, Dallegri F (2005) Dexamethasone-induced apoptosis of human monocytes exposed to immune complexes. Intervention of CD95- and XIAP-dependent pathways. Int J Immunopathol Pharmacol 18:403–415

    PubMed  CAS  Google Scholar 

  31. Conti P, Feliciani C, Barbacane RC, Frydas S, Placido FC, Cataldo I, Reale M (1999) Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo. Calcif Tissue Int 64:57–62

    Article  PubMed  CAS  Google Scholar 

  32. Selye H (1962) Calciphylaxis. University of Chicago Press, Chicago

    Google Scholar 

  33. Selye H, Somogyi A, Mecs I (1986) Inhibition of local calcergy by topical application of calciphylactic challengers. Calcif Tissue Res 2:67–76

    Article  Google Scholar 

  34. Gabbiani G, Jacqmin ML, Richard RM (1966) Soft-tissue calcification induced by rare earth metals and its prevention by sodium pyrophosphate. Br J Pharmacol 27:1–9

    CAS  Google Scholar 

  35. Oppenheim JJ, Zachariae CO, Mukaida N, Matsushima K (1991) Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu Rev Immunol 9:617–648

    PubMed  CAS  Google Scholar 

  36. Luther SA, Cyster JG (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2:102–107

    Article  PubMed  CAS  Google Scholar 

  37. Yamaki K, Uchida H, Li X, Yanagisawa R, Takano H, Hayashi H, Mori Y, Yoshino S (2005) Effect of varying types of anti-arthritic drugs on Th1 and Th2 immune responses in mice. Int J Immunopathol Pharmacol 18:133–144

    PubMed  CAS  Google Scholar 

  38. Lanzilli G, Falchetti R, Tricarico M, Ungheri D, Fuggetta MP (2005) In vitro effects of an immunostimulating bacterial lysate on human lymphocyte function. Int J Immunopathol Pharmacol 18:245–254

    PubMed  CAS  Google Scholar 

  39. Chensue SW, Warmington KS, Allenspach EJ, Lu B, Gerard C, Kunkel SL, Lukacs NW (1999) Differential expression and cross-regulatory function of RANTES during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granulomatous inflammation. J Immunol 163:165–173

    PubMed  CAS  Google Scholar 

  40. Hebert CA (1999) Chemokines in Disease: Biology and Clinical Research. Humana Press, Totowa, NJ

    Google Scholar 

  41. Lo Iacono M, Cavallo F, Quaglino E, Rolla S, Iezzi M, Pupa SM, De Giovanni C, Lollini PL, Musiani P, Forni G, Calogero RA (2005) A limited autoimmunity to p185neu elicited by DNA and allogeneic cell vaccine hampers the progression of preneoplastic lesions in HER-2/NEU transgenic mice. Int J Immunopathol Pharmacol 18:351–363

    PubMed  CAS  Google Scholar 

  42. Alexandrakis MG, Passam FH, Pappa CA, Damilakis J, Tsirakis G, Kandidaki E, Passam AM, Stathopoulos EN, Kyriakou DS (2005) Serum evaluation of angiogenic cytokine basic fibroblast growth factor, hepatocyte growth factor and TNF-alpha in patients with myelodysplastic syndromes: correlation with bone marrow microvascular density. Int J Immunopathol Pharmacol 18:287–295

    PubMed  CAS  Google Scholar 

  43. Fioriti D, Penta M, Mischitelli M, Degener AM, Pierangeli A, Gentile V, Nicosia R, Gallinelli C, Chiarini F, Pietropaolo V (2005) Interstitial cystitis and infectious agents. Int J Immunopathol Pharmacol 18:799–804

    PubMed  CAS  Google Scholar 

  44. Marasini B, Massarotti M, Cossutta R (2005) Scleroderma heart disease. Int J Immunopathol Pharmacol 18:609–614

    PubMed  CAS  Google Scholar 

  45. Tsukishiro S, Suzumori N, Nishikawa H, Arakawa A, Suzumori K (2006) Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder. Gynecol Oncol 102:542–545

    Article  PubMed  CAS  Google Scholar 

  46. Belli R, Amerio P, Brunetti L, Orlando G, Toto P, Proietto G, Vacca M, Tulli A (2005) Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin. Int J Immunopathol Pharmacol 18:497–502

    PubMed  CAS  Google Scholar 

  47. Stanczyk J, Kowalski ML, Grzegorczyk J, Szkudlinska B, Jarzebska M, Marciniak M, Synder M (2005) RANTES and chemotactic activity in synovial fluids from patients with rheumatoid arthritis and osteoarthritis. Mediators Inflamm 2005:343–348

    Article  PubMed  CAS  Google Scholar 

  48. Totaro R, Passacantando A, Russo T, Parzanese I, Rascente M, Marini C, Tonietti G, Carolei A (2005) Effects of interferon beta, cyclophosphamide and azathioprine on cytokine profile in patients with multiple sclerosis. Int J Immunopathol Pharmacol 18:377–383

    PubMed  CAS  Google Scholar 

  49. Garcia-Vicuna R, Gomez-Gaviro MV, Dominguez-Luis MJ, Pec MK, Gonzalez-Alvaro I, Alvaro-Gracia JM, Diaz-Gonzalez F (2004) CC and CXC chemokine receptors mediate migration, proliferation, and matrix metalloproteinase production by fibroblast-like synoviocytes from rheumatoid arthritis patients. Arthritis Rheum 50:3866–3877

    Article  PubMed  CAS  Google Scholar 

  50. Licastro F, Chiappelli M, Ruscica M, Carnelli V, Corsi MM (2005) Altered cytokine and acute phase response protein levels in the blood of children with Down syndrome: relationship with dementia of Alzheimer’s type. Int J Immunopathol Pharmacol 18:165–172

    PubMed  CAS  Google Scholar 

  51. Waku M, Napolitano L, Clementini E, Staniscia T, Spagnolli C, Andama A, Kasiriye P, Innocenti P (2005) Risk of cancer onset in sub-Saharan Africans affected with chronic gastrointestinal parasitic diseases. Int J Immunopathol Pharmacol 18:503–511

    PubMed  CAS  Google Scholar 

  52. Yano S, Mentaverri R, Kanuparthi D, Bandyopadhyay S, Rivera A, Brown EM, Chattopadhyay N (2005) Functional expression of beta-chemokine receptors in osteoblasts: role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. Endocrinology 146:2324–2335

    Article  PubMed  CAS  Google Scholar 

  53. Barnes DA, Tse J, Kaufhold M, Owen M, Hesselgesser J, Strieter R, Horuk R, Perez HD (1998) Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Invest 101:2910–2919

    Article  PubMed  CAS  Google Scholar 

  54. Concoff AL, Kalunian KC (1999) What is the relation between crystals and osteoarthritis? Curr Opin Rheumatol 11:436–440

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    L. N. Shanmugham

  2. Immunology Division, Department of Oncology and Neuroscience, University of Chieti-Pescara, 66100, Chieti, Italy

    C. Petrarca, M. De Colli & P. Conti

  3. Department of Medicine and Aging, Medical School, University of Chieti-Pescara, 66100, Chieti, Italy

    M. L. Castellani & V. Salini

  4. Laboratory of Parasitology, Veterinary Faculty, Aristotle University, Thessaloniki, Greece

    I. Simeonidou & S. Frydas

  5. Clinical of Infectious Diseases, Medical School, University of Chieti-Pescara, 66100, Chieti, Italy

    J. Vecchiet & K. Falasca

  6. Dental School, University of Chieti-Pescara, Via dei Vestini 32, 66100, Chieti, Italy

    S. Tetè

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  1. M. L. Castellani
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Correspondence to P. Conti.

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Castellani, M.L., Shanmugham, L.N., Petrarca, C. et al. Expression and Secretion of RANTES (CCL5) in Granulomatous Calcified Tissue before and after Lipopolysaccharide Treatment In Vivo . Calcif Tissue Int 80, 60–67 (2007). https://doi.org/10.1007/s00223-006-0115-2

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