Skip to main content
Log in

Upregulation of type I interleukin−1 receptor after traumatic spinal cord injury in adult rats

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Post-traumatic inflammation response has been implicated in secondary injury mechanisms after spinal cord injury (SCI). Interleukin-1 (IL-1) is a key inflammatory mediator that is increasingly expressed after SCI. The action of IL-1 is mediated through its functional receptor, type I interleukin-1 receptor (IL-1RI). However, whether this receptor is expressed after SCI remains to be elucidated. In the present study, the temporospatial expression of IL-1RI was detected in rats that received a moderate contusive SCI (a 10 g rod dropped at a height of 12.5 mm) at the ninth to tenth thoracic vertebral level using a widely used New York University impact device. Our study demonstrated that IL-1RI was slightly increased at 4 h post-injury compared to the normal or sham-operated controls, reached the peak at 8 h at mRNA level (4.44-fold, P<0.01) and 1 d at protein level (2.62-fold, P<0.01). IL-1RI remained at its elevated levels for a relatively long duration (4 h–7 days). Spatially, IL-1RI was observed throughout the entire length of a 10 mm-long cord segment containing the injury epicenter. Colocalization of IL-1RI was found in neurons, oligodendrocytes, astrocytes, and activated microglia. Our results suggest that the elevated expression of IL-1RI after SCI may contribute to posttraumatic inflammation responses of IL-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Reference

  1. Albrecht PJ, Dahl JP, Stoltzfus OK, Levenson R, Levison SW (2002) Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival. Exp Neurol 173:46–62

    Article  PubMed  CAS  Google Scholar 

  2. Bartholdi D, Schwab ME (1995) Methylprednisolone inhibits early inflammatory processes but not ischemic cell death after experimental spinal cord lesion in the rat. Brain Res 672:177–186

    Article  PubMed  CAS  Google Scholar 

  3. Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transaction. Exp Neurol 139:244–256

    Article  PubMed  CAS  Google Scholar 

  4. Basu A, Krady JK, Levison SW (2004) Interleukin-1: a master regulator of neuroinflammation. J Neurosci Res 78:151–156

    Article  PubMed  CAS  Google Scholar 

  5. Basu A, Krady JK, O’Malley M, Styren SD, DeKosky ST, Levison SW (2002) The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci 22:6071–6082

    PubMed  CAS  Google Scholar 

  6. Basu A, Lazovic J, Krady JK, Mauger DT, Rothstein RP Smith MB, Levison SW (2005) Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. J Cereb Blood Flow Metab 25:17–29

    Article  PubMed  CAS  Google Scholar 

  7. Berkenbosch F, van OJ, del RA, Tilders F, Besedovsky H (1987) Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1 Science. 238:524–526

    Article  PubMed  CAS  Google Scholar 

  8. Besedovsky H, del RA, Sorkin E, Dinarello CA (1986) Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 233:652–654

    Article  PubMed  CAS  Google Scholar 

  9. Blasi F, Riccio M, Brogi A, Strazza M, Taddei ML, Romagnoli S, Luddi A, D’Angelo R, Santi S, Costantino-Ceccarini E, Melli M (1999) Constitutive expression of interleukin-1beta (IL-1beta) in rat oligodendrocytes. Biol Chem 380:259–264

    Article  PubMed  CAS  Google Scholar 

  10. Bluthe RM, Laye S, Michaud B, Combe C, Dantzer R, Parnet P (2000) Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. Eur J Neurosci 12:4447–4456

    Article  PubMed  CAS  Google Scholar 

  11. Bossu P, Visconti U, Ruggiero P, Macchia G, Muda M, Bertini R, Bizzarri C, Colagrande A, Sabbatini V, Maurizi G (1995) Transfected type II interleukin-1 receptor impairs responsiveness of human keratinocytes to interleukin-1. Am J Pathol 147:1852–1861

    PubMed  CAS  Google Scholar 

  12. Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ (2001) Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 21:5528–5534

    PubMed  CAS  Google Scholar 

  13. Brenneman DE, Hill JM, Glazner GW, Gozes I, Phillips TW (1995) Interleukin-1 alpha and vasoactive intestinal peptide: enigmatic regulation of neuronal survival. Int J Dev Neurosci 13:187–200

    Article  PubMed  CAS  Google Scholar 

  14. Chung IY, Benveniste EN (1990) Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J Immunol 144:2999–3007

    PubMed  CAS  Google Scholar 

  15. Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M, Giri JG, Dower SK, Sims JE, Mantovani A (1993) Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science 261:472–475

    Article  PubMed  CAS  Google Scholar 

  16. Cremona S, Laye S, Dantzer R, Parnet P (1998) Blockade of brain type II interleukin-1 receptors potentiates IL1beta-induced anorexia in mice. Neurosci Lett 246:101–104

    Article  PubMed  CAS  Google Scholar 

  17. Davies CA, Loddick SA, Toulmond S, Stroemer RP, Hunt J, Rothwell NJ (1999) The progression and topographic distribution of interleukin-1beta expression after permanent middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 19:87–98

    Article  PubMed  CAS  Google Scholar 

  18. Dziegielewska KM, Moller JE, Potter AM, Ek J, Lane MA, Saunders NR (2000) Acute-phase cytokines IL-1beta and TNF-alpha in brain development. Cell Tissue Res 299:335–345

    PubMed  CAS  Google Scholar 

  19. Eriksson C, Van Dam AM, Lucassen PJ, Bol JG, Winblad B, Schultzberg M (1999) Immunohistochemical localization of interleukin-1beta, interleukin−1 receptor antagonist and interleukin-1beta converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid. Neuroscience 93:915–930

    Article  PubMed  CAS  Google Scholar 

  20. Giulian D, Young DG, Woodward J, Brown DC, Lachman LB (1988) Interleukin-1 is an astroglial growth factor in the developing brain. J Neurosci 8:709–714

    PubMed  CAS  Google Scholar 

  21. Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C (2001) An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods 25:386–401

    Article  PubMed  CAS  Google Scholar 

  22. Gruner JA (1992) A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9:123–126

    Article  PubMed  CAS  Google Scholar 

  23. Hsu CY, Dimitrijevic MR (1990) Methylprednisolone in spinal cord injury: the possible mechanism of action. J Neurotrauma 7:115–119

    PubMed  CAS  Google Scholar 

  24. John GR, Lee SC, Brosnan CF (2003) Cytokines: powerful regulators of glial cell activation. Neuroscientist 9:10–22

    Article  PubMed  CAS  Google Scholar 

  25. Johnson RW, Arkins S, Dantzer R, Kelley KW (1997) Hormones, lymphohemopoietic cytokines and the neuroimmune axis. Comp Biochem Physiol A Physiol 116:183–201

    Article  PubMed  CAS  Google Scholar 

  26. Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159

    Article  PubMed  CAS  Google Scholar 

  27. Labow M, Shuster D, Zetterstrom M, Nunes P, Terry R, Cullinan EB, Bartfai T, Solorzano C, Moldawer LL, Chizzonite R, McIntyre KW (1997) Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice. J Immunol 159:2452–2461

    PubMed  CAS  Google Scholar 

  28. Lee SC, Liu W, Brosnan CF, Dickson DW (1994) GM-CSF promotes proliferation of human fetal and adult microglia in primary cultures. Glia 12:309–318

    Article  PubMed  CAS  Google Scholar 

  29. Li C, Zienkiewicz J, Hawiger J (2005) Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathway. J Biol Chem 280:26152–26159

    Article  PubMed  CAS  Google Scholar 

  30. Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW (2004) Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89:1092–1100

    Article  PubMed  CAS  Google Scholar 

  31. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  32. Loddick SA, Rothwell NJ (1996) Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 16:932–940

    Article  PubMed  CAS  Google Scholar 

  33. Mason JL, Suzuki K, Chaplin DD, Matsushima GK (2001) Interleukin-1beta promotes repair of the CNS. J Neurosci 21:7046–7052

    PubMed  CAS  Google Scholar 

  34. Nesic O, Xu GY, McAdoo D, High KW, Hulsebosch C, Perez-Pol R (2001) IL-1 receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury. J Neurotrauma 18:947–956

    Article  PubMed  CAS  Google Scholar 

  35. Norris JG, Tang LP, Sparacio SM, Benveniste EN (1994) Signal transduction pathways mediating astrocyte IL−6 induction by IL−1 beta and tumor necrosis factor-alpha. J Immunol 152:841–850

    PubMed  CAS  Google Scholar 

  36. O’Neill LA, Greene C (1998) Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol 63:650–657

    PubMed  CAS  Google Scholar 

  37. Pan JZ, Ni L, Sodhi A, Aguanno A, Young W, Hart RP (2002) Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. J Neurosci Res 68:315–322

    Article  PubMed  CAS  Google Scholar 

  38. Parish CL, Finkelstein DI, Tripanichkul W, Satoskar AR, Drago J, Horne MK (2002) The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice. J Neurosci 22:8034–8041

    PubMed  CAS  Google Scholar 

  39. Parker LC, Luheshi GN, Rothwell NJ, Pinteaux E (2002) IL-1 beta signalling in glial cells in wildtype and IL-1RI deficient mice. Br J Pharmacol 136:312–320

    Article  PubMed  CAS  Google Scholar 

  40. Pearson VL, Rothwell NJ, Toulmond S (1999) Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death. Glia 25:311–323

    Article  PubMed  CAS  Google Scholar 

  41. Pinteaux E, Parker LC, Rothwell NJ, Luheshi GN (2002) Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells. J Neurochem 83:754–763

    Article  PubMed  CAS  Google Scholar 

  42. Rothwell NJ, Luheshi GN (2000) Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 23:618–625

    Article  PubMed  CAS  Google Scholar 

  43. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475

    Article  PubMed  CAS  Google Scholar 

  44. Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W (1987) Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science 238:522–524

    Article  PubMed  CAS  Google Scholar 

  45. Sims JE, Gayle MA, Slack JL, Alderson MR, Bird TA, Giri JG, Colotta F, Re F, Mantovani A, Shanebeck K (1993) Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci USA 90:6155–6159

    Article  PubMed  CAS  Google Scholar 

  46. Sung CS, Wen ZH, Chang WK, Ho ST, Tsai SK, Chang YC, Wong CS (2004) Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. Brain Res 1015:145–153

    Article  PubMed  CAS  Google Scholar 

  47. Vitkovic L, Bockaert J, Jacque C (2000) “Inflammatory” cytokines: neuromodulators in normal brain? J Neurochem 74:457–471

    Article  PubMed  CAS  Google Scholar 

  48. Wang CX, Olschowka JA, Wrathall JR (1997) Increase of interleukin-1beta mRNA and protein in the spinal cord following experimental traumatic injury in the rat. Brain Res 759:190–196

    Article  PubMed  CAS  Google Scholar 

  49. Xu J, Fan G, Chen S, Wu Y, Xu XM, Hsu CY (1998) Methylprednisolone inhibition of TNF-alpha expression and NF-kB activation after spinal cord injury in rats. Brain Res Mol Brain Res 59:135–142

    Article  PubMed  CAS  Google Scholar 

  50. Yan P, Liu N, Kim GM, Xu J, Xu J, Li Q, Hsu CY, Xu XM (2003) Expression of the type 1 and type 2 receptors for tumor necrosis factor after traumatic spinal cord injury in adult rats. Exp Neurol 183:286–297

    Article  PubMed  CAS  Google Scholar 

  51. Yan P, Xu J, Li Q, Chen S, Kim GM, Hsu CY, Xu XM (1999) Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats. J Neurosci 19:9355–9363

    PubMed  CAS  Google Scholar 

  52. Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN (2004) Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine 29:966–971

    Article  PubMed  Google Scholar 

  53. Yang L, Jones NR, Blumbergs PC, Van Den HC, Moore EJ, Manavis J, Sarvestani GT, Ghabriel MN (2005) Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat. J Clin Neurosci 12:276–284

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the grant from Major State Basic Research Development Program of China (973 Project) (2003CB515302) and Shanghai Science Development Fund (02JC14014). The authors thank Zhen Guan, research associate from the Spinal Cord Injury Research Center, Ohio State University, for his technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xiao-Ming Xu or Pei-Hua Lu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, XF., Huang, LD., Yu, PP. et al. Upregulation of type I interleukin−1 receptor after traumatic spinal cord injury in adult rats. Acta Neuropathol 111, 220–228 (2006). https://doi.org/10.1007/s00401-005-0016-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-005-0016-x

Keywords

Navigation