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Pflügers Archiv - European Journal of Physiology

, Volume 471, Issue 2, pp 301–311 | Cite as

Role of CINC-1 and CXCR2 receptors on LPS-induced fever in rats

  • Lívia Harumi Yamashiro
  • Glória Emília Petto de Souza
  • Denis de Melo SoaresEmail author
Integrative Physiology
  • 226 Downloads
Part of the following topical collections:
  1. Integrative Physiology

Abstract

The classic model of fever induction is based on the administration of lipopolysaccharide (LPS) from Gram-negative bacteria in experimental animals. LPS-induced fever results in the synthesis/release of many mediators that assemble an LPS-fever cascade. We have previously demonstrated that cytokine-induced neutrophil chemoattractant (CINC)-1, a Glu-Leu-Arg (ELR) + chemokine, centrally administered to rats, induces fever and increases prostaglandin E2 in the cerebrospinal fluid. We now attempt to investigate the involvement of CINC-1 and its functional receptor CXCR2 on the fever induced by exogenous and endogenous pyrogens in rats. We also investigated the effect of reparixin, an allosteric inhibitor of CXCR1/CXCR2 receptors, on fever induced by either systemic administration of LPS or intracerebroventricular injection of CINC-1, as well as TNF-α, IL-1β, IL-6, or ET-1, known mediators of febrile response. Our results show increased CINC-1 mRNA expression in the liver, hypothalamus, CSF, and plasma following LPS injection. Moreover, reparixin administered right before CINC-1 or LPS abolished the fever induced by CINC-1 and significantly reduced the response induced by LPS. In spite of these results, reparixin does not modify the fever induced by IL-1β, TNF-α, and IL-6, but significantly reduces ET-1-induced fever. Therefore, it is plausible to suggest that CINC-1 might contribute to LPS-induced fever in rats by activating CXCR2 receptor on the CNS. Moreover, it can be hypothesized that CINC-1 is placed upstream TNF-α, IL-1β, and IL-6 among the prostaglandin-dependent fever-mediator cascade and amidst the prostaglandin-independent synthesis pathway of fever.

Keywords

CINC-1 Reparixin CXCR2 receptor LPS Fever 

Notes

Acknowledgements

We are most grateful to Aparecida Rosa da Silva, Miriam C. C. Melo, and Juliana Vercesi for their expert technical assistance.

Funding

This study was funded by FAPESP (Proc. 050/2008), FAPESB (RED014/2013), and CNPq (Proc. 302575/2015-4).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experiments were previously approved by the Ethical Commission of Ethics in Animal Research of the College of Medicine of Ribeirão Preto University of São Paulo (protocol no. 050/2008) and were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research (1996).

This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Anthony D, Dempster R, Fearn S, Clements J, Wells G, Perry VH, Walker K (1998) CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown. Curr Biol 8(16):923–926CrossRefGoogle Scholar
  2. 2.
    Barichello T, Lemos JC, Generoso JS, Cipriano AL, Milioli GL, Marcelino DM, Vuolo F, Petronilho F, Dal-Pizzol F, Vilela MC, Teixeira AL (2011) Oxidative stress, cytokine/chemokine and disruption of blood-brain barrier in neonate rats after meningitis by Streptococcus agalactiae. Neurochem Res 36(10):1922–1930CrossRefGoogle Scholar
  3. 3.
    Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313CrossRefGoogle Scholar
  4. 4.
    Bertini R, Allegretti M, Bizzarri C, Moriconi A, Locati M, Zampella G, Cervellera MN, di Cioccio V, Cesta MC, Galliera E, Martinez FO, di Bitondo R, Troiani G, Sabbatini V, D’Anniballe G, Anacardio R, Cutrin JC, Cavalieri B, Mainiero F, Strippoli R, Villa P, di Girolamo M, Martin F, Gentile M, Santoni A, Corda D, Poli G, Mantovani A, Ghezzi P, Colotta F (2004) Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A 101:11791–11796CrossRefGoogle Scholar
  5. 5.
    Boulant JA (2006) Counterpoint: heat-induced membrane depolarization of hypothalamic neurons: an unlikely mechanism of central thermosensitivity. Am J Phys Regul Integr Comp Phys 290:R1481–R1484Google Scholar
  6. 6.
    Brandolini L, Benedetti E, Ruffini PA, Russo R, Cristiano L, Antonosante A, d’Angelo M, Castelli V, Giordano A, Allegretti M, Cimini A (2017) CXCR1/2 pathways in paclitaxel-induced neuropathic pain. Oncotarget 8:23188–23201Google Scholar
  7. 7.
    Budick-Harmelin N, Dudas J, Demuth J, Madar Z, Ramadori G, Tirosh O (2010) Triglycerides potentiate the inflammatory response in rat Kupffer cells. Antioxid Redox Signal 10(12):2009–2022CrossRefGoogle Scholar
  8. 8.
    Calkins CM, Bensard DD, Shames BD, Pulido EJ, Abraham E, Fernandez N, Meng X, Dinarello CA, McIntyre RC Jr (2002) IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia. J Endotoxin Res 8(1):59–67Google Scholar
  9. 9.
    Campbell SJ, Hughes PM, Iredale JP, Wilcockson DC, Waters S, Docagne F, Perry VH, Anthony DC (2003) CINC-1 is identified as an acute-phase protein induced by focal brain injury causing leukocyte mobilization and liver injury. FASEB J 17(9):1168–1170CrossRefGoogle Scholar
  10. 10.
    Chapman RW, Minnicozzi M, Celly CS, Phillips JE, Kung TT, Hipkin RW, Fan X, Rindgen D, Deno G, Bond R, Gonsiorek W, Billah MM, Fine JS, Hey JA (2007) A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther 322(2):486–493CrossRefGoogle Scholar
  11. 11.
    Consiglio AR, Lucion AB (2000) Technique for collecting cerebrospinal fluid in the cisterna magna of non-anesthetized rats. Brain Res Protocol 5:109–114CrossRefGoogle Scholar
  12. 12.
    Davatelis G, Wolpe SD, Sherry B, Dayer JM, Chicheportiche R, Cerami A (1989) Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Science 243:1066–1068CrossRefGoogle Scholar
  13. 13.
    Dinarello CA (1984) Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med 311(22):1413–1418CrossRefGoogle Scholar
  14. 14.
    Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, Figari IS, Palladino MA Jr, O’Connor JV (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 163(6):1433–1450CrossRefGoogle Scholar
  15. 15.
    Dunstan CN, Salafranca MN, Adhikari S, Xia Y, Feng L, Harrison JK (1996) Identification of two rat genes orthologous to the human interleukin-8 receptors. J Biol Chem 271:32770–32776CrossRefGoogle Scholar
  16. 16.
    Fabricio AS, Tringali G, Pozzoli G, Melo MC, Vercesi JA, Souza GE, Navarra P (2006) Interleukin-1 mediates endothelin-1-induced fever and prostaglandin production in the preoptic area of rats. Am J Phys Regul Integr Comp Phys 290(6):R1515–R1523Google Scholar
  17. 17.
    Fabricio AS, Veiga FH, Cristofoletti R, Navarra P, Souza GE (2005) The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats. Am J Phys Regul Integr Comp Phys 288(3):R671–R677Google Scholar
  18. 18.
    Fabricio AS, Silva CA, Rae GA, D’Orléans-Juste P, Souza GE (1998) Essential role for endothelin ET(B) receptors in fever induced by LPS (E. coli) in rats. Br J Pharmacol 125(3):542–548CrossRefGoogle Scholar
  19. 19.
    Girard JP, Moussion C, Forster R (2012) HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol 12:762–773CrossRefGoogle Scholar
  20. 20.
    Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, Trichereau J, Paolino M, Qadri F, Plehm R, Klaere S, Komnenovic V, Mimata H, Yoshimatsu H, Takahashi N, von Haeseler A, Bader M, Kilic SS, Ueta Y, Pifl C, Narumiya S, Penninger JM (2009) Central control of fever and female body temperature by RANKL/RANK. Nature 462:505–509CrossRefGoogle Scholar
  21. 21.
    Harden LM, Kent S, Pittman QJ, Roth J (2015) Fever and sickness behavior: friend or foe? Brain Behav Immun 50:322–333.  https://doi.org/10.1016/j.bbi.2015.07.012 CrossRefGoogle Scholar
  22. 22.
    Harré EM, Roth J, Pehl U, Kueth M, Gerstberger R, Hübschle T (2002) Selected contribution: role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats. J Appl Physiol 92:2657–2666CrossRefGoogle Scholar
  23. 23.
    Helle M, Brakenhoff JPJ, De Groot ER, Aarden LA (1988) Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol 18:957–959CrossRefGoogle Scholar
  24. 24.
    Kluger MJ (1991) Fever: role of pyrogens and cryogens. Physiol Rev 71(1):93–127CrossRefGoogle Scholar
  25. 25.
    Khanam A, Trehanpati N, Riese P, Rastogi A, Guzman CA, Sarin SK (2017) Blockade of neutrophil’s chemokine receptors CXCR1/2 abrogate liver damage in acute-on-chronic liver failure. Front Immunol 8:464.  https://doi.org/10.3389/fimmu.2017.00464 CrossRefGoogle Scholar
  26. 26.
    Loram LC, Themistocleous AC, Fick LG, Kamerman PR (2007) The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia. Can J Physiol Pharmacol 85(6):613–620CrossRefGoogle Scholar
  27. 27.
    Machado RR, Soares DM, Proudfoot AE, Souza GEP (2007) CCR1 and CCR5 chemokine receptors are involved in fever induced by LPS (E. coli) and RANTES in rats. Brain Res 1161:21–31CrossRefGoogle Scholar
  28. 28.
    Michalak S, Wender M, Michalowska-Wender G, Kozubski W (2010) Blood-brain barrier breakdown and cerebellar degeneration in the course of experimental neoplastic disease. Are circulating cytokine-induced neutrophil chemoattractant-1 (CINC-1) and -2alpha(CINC-2alpha) the involved mediators? Folia Neuropathol 48(2):93–103Google Scholar
  29. 29.
    Moriconi A, Cesta MC, Cervellera MN, Aramini A, Coniglio S, Colagioia S, Beccari AR, Bizzarri C, Cavicchia MR, Locati M et al (2007) Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem 50:3984–4002CrossRefGoogle Scholar
  30. 30.
    Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K et al (2000) International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52:145–176Google Scholar
  31. 31.
    Nakagawa H, Ikesue A, Hatakeyama S, Kato H, Gotoda T, Komorita N, Watanabe K, Miyai H (1993) Production of an interleukin-8-like chemokine by cytokine-stimulated rat NRK-49F fibroblasts and its suppression by anti-inflammatory steroids. Biochem Pharmacol 45:1425–1430CrossRefGoogle Scholar
  32. 32.
    Nakamura K (2011) Central circuitries for body temperature regulation and fever. Am J Phys Regul Integr Comp Phys 301(5):R1207–R1228Google Scholar
  33. 33.
    Nguyen D, Stangel M (2001) Expression of the chemokine receptors CXCR1 and CXCR2 in rat oligodendroglial cells. Brain Res Dev Brain Res 128(1):77–81CrossRefGoogle Scholar
  34. 34.
    National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011) Guide for the care and use of laboratory animals, 8th edn. National Academies Press, Washington, DCGoogle Scholar
  35. 35.
    Osborn O, Sanchez-Alavez M, Dubins JS, Gonzalez AS, Morrison B, Hadcock JR, Bartfai T (2011) Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue. Cytokine 53(3):311–319CrossRefGoogle Scholar
  36. 36.
    Ostberg JR, Repasky EA (2007) Emerging evidence indicates that physiologically relevant thermal stress regulates dendritic cell function. Cytokine 39(1):84–96CrossRefGoogle Scholar
  37. 37.
    Ott D, Murgott J, Rafalzik S, Wuchert F, Schmalenbeck B, Roth J, Gerstberger R (2010) Neurons and glial cells of the rat organum vasculosum laminae terminalis directly respond to lipopolysaccharide and pyrogenic cytokines. Brain Res 1363:93–106CrossRefGoogle Scholar
  38. 38.
    Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic Press, New YorkGoogle Scholar
  39. 39.
    Planagumà A, Domènech T, Pont M, Calama E, García-González V, López R, Aulí M, López M, Fonquerna S, Ramos I, de Alba J, Nueda A, Prats N, Segarra V, Miralpeix M, Lehner MD (2015) Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation. Pulm Pharmacol Ther 34:37–45CrossRefGoogle Scholar
  40. 40.
    Podolin PL, Bolognese BJ, Foley JJ, Schmidt DB, Buckley PT, Widdowson KL, Jin Q, White JR, Lee JM, Goodman RB, Hagen TR, Kajikawa O, Marshall LA, Hay DW, Sarau HM (2002) A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol 169(11):6435–6444CrossRefGoogle Scholar
  41. 41.
    Romanovsky AA, Ivanov AI, Shimansky YP (2002) Selected contribution: ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality. J Appl Physiol 92(6):2667–2679CrossRefGoogle Scholar
  42. 42.
    Roth J, De Souza GE (2001) Fever induction pathways: evidence from responses to systemic or local cytokine formation. Braz J Med Biol Res 34(3):301–314CrossRefGoogle Scholar
  43. 43.
    Rummel C, Barth SW, Voss T, Korte S, Gerstberger R, Hübschle T, Roth J (2005) Localized vs. systemic inflammation in Guinea pigs: a role for prostaglandins at distinct points of the fever induction pathways? Am J Phys Regul Integr Comp Phys 289(2):R340–R347Google Scholar
  44. 44.
    Soares DM, Hiratsuka Veiga-Souza F, Fabrício AS, Javier Miñano F, Petto Souza GE (2006) CCL3/macrophage inflammatory protein-1alpha induces fever and increases prostaglandin E2 in cerebrospinal fluid of rats: effect of antipyretic drugs. Brain Res 1109(1):83–92CrossRefGoogle Scholar
  45. 45.
    Soares DM, Machado RR, Yamashiro LH, Melo MC, Souza GEP (2008) CINC-1 induces fever by a prostaglandin depending pathway. Brain Res 1233:79–88CrossRefGoogle Scholar
  46. 46.
    Souza GEP, Cardoso RA, Melo MCC, Fabricio ASC, Silva VMS, Lora M, De Brum-Fernandes AJ, Ferreira SH, Zampronio AR (2002) Comparative study of antipyretic profiles of indomethacin and dipyrone in rats. Inflamm Res 51:24–32CrossRefGoogle Scholar
  47. 47.
    Souza DG, Bertini R, Vieira AT, Cunha FQ, Poole S, Allegretti M, Colotta F, Teixeira MM (2004) Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. Br J Pharmacol 143:132–142CrossRefGoogle Scholar
  48. 48.
    Stojilkovic SS, Catt KJ (1996) Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. Front Neuroendocrinol 17(3):327–369CrossRefGoogle Scholar
  49. 49.
    Strijbos PJ, Hardwick AJ, Relton JK, Carey F, Rothwell NJ (1992) Inhibition of central actions of cytokines on fever and thermogenesis by lipocortin-1 involves CRF. Am J Phys 263:E632–E636Google Scholar
  50. 50.
    Takahashi K, Ghatei MA, Jones PM, Murphy JK, Lam HC, O’Halloran DJ, Bloom SR (1991) Endothelin in human brain and pituitary gland: comparison with rat. J Cardiovasc Pharmacol 17(Suppl 7):S101–S103CrossRefGoogle Scholar
  51. 51.
    Tavares E, Miñano FJ (2000) RANTES: a new prostaglandin dependent endogenous pyrogen in the rat. Neuropharmacology 39(12):2505–2513CrossRefGoogle Scholar
  52. 52.
    Vardam TD, Zhou L, Appenheimer MM, Chen Q, Wang WC, Baumann H, Evans SS (2006) Regulation of a lymphocyte-endothelial-IL-6 trans-signaling axis by fever-range thermal stress: hot spot of immune surveillance. Cancer Immunol Immunother 55(3):292–298CrossRefGoogle Scholar
  53. 53.
    Wuyts A, Van Osselaer N, Haelens A, Samson I, Herdewijn P, Ben-Baruch A, Oppenheim JJ, Proost P, Van Damme J (1997) Characterization of synthetic human granulocyte chemotactic protein 2: usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties. Biochemistry 36(9):2716–2723CrossRefGoogle Scholar
  54. 54.
    Yan X, Xiu F, An H, Wang X, Wang J, Cao X (2007) Fever range temperature promotes TLR4 expression and signaling in dendritic cells. Life Sci 80:307–313CrossRefGoogle Scholar
  55. 55.
    Yoshimi H, Kawano Y, Akabane S, Ashida T, Yoshida K, Kinoshita O, Kuramochi M, Omae T (1991) Immunoreactive endothelin-1 contents in brain regions from spontaneously hypertensive rats. J Cardiovasc Pharmacol 17(Suppl 7):S417–S419CrossRefGoogle Scholar
  56. 56.
    Zampronio AR, Soares DM, Souza GEP (2015) Central mediators involved in the febrile response: effects of antipyretic drugs. Temperature 2(4):506–521CrossRefGoogle Scholar
  57. 57.
    Zampronio AR, Melo MCC, Hopkins SJ, Souza GEP (2000) Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF). Inflamm Res 49:1–7CrossRefGoogle Scholar
  58. 58.
    Zampronio AR, Souza GEP, Silva CAA, Cunha FQ, Ferreira SH (1994) Interleukin-8 induces fever by a prostaglandin-independent mechanism. Am J Phys 266:R1670–R1674Google Scholar
  59. 59.
    Zarbock A, Allegretti M, Ley K (2008) Therapeutic inhibition of CXCR2 by reparixin attenuates acute lung injury in mice. Br J Pharmacol 155(3):357–364CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical ScienceUniversity of São PauloRibeirão PretoBrazil
  2. 2.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkeleyUSA
  3. 3.Faculdade de FarmáciaUniversidade Federal da BahiaSalvadorBrazil

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