Inflammopharmacology

, Volume 22, Issue 1, pp 37–44 | Cite as

Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats

  • Jalal Zaringhalam
  • Zeinab Akhtari
  • Akram Eidi
  • Ali Haeri Ruhani
  • Elaheh Tekieh
Research Article

Abstract

Objects and design

Regarding to anti-inflammatory role of interleukin (IL) 10, its inhibitory effects on p38MAPK activity and, different pro and anti-inflammatory roles of activated p38MAPK in cells, this study was aimed to investigate relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects variation of hyperalgesia during different stages of arthritis in rats.

Materials and methods

Adjuvant arthritis (AA) was induced by a single subcutaneous injection of complete Freund’s adjuvant into the rats’ hind paw. Behavioral and inflammatory responses were assessed at 0, 3, 7, 14, and 21 days of study. Receptor and other protein enzyme expression variations were detected by western blotting. Anti-IL10 and p38MAPK inhibitor were administered daily during the 21 days of study.

Result

Daily treatment with anti-IL10 antibody significantly increased paw edema and hyperalgesia in the AA group compared with the AA control group. Administration of anti-IL10 antibody caused significant increase in the ratio of phosphorylated p38 to p38MAPK enzyme level expression on 14th and 21st days of study compared with the AA control group.

Conclusion

Our study confirmed that a part of anti- inflammatory effects of serum IL10 during AA inflammation was mediated via inhibition of p38MAPK enzyme phosphorylation. Moreover, these findings suggest that increase in the level of spinal mu opioid receptor expression during AA inflammation is not mediated via the direct effect of serum IL10 on spinal p38MAPK.

Keywords

IL10 Arthritis Hyperalgesia Mu opioid receptor p38MAPK 

References

  1. Akhtari Z, Zaringhalam J, Eidi A, Manaheji H, Tekieh E (2012) Bidirectional effects of serum TNFα level and spinal P38MAPK phosphorylation on hyperalgesia variation during CFA-induced arthritis. EXCLI J 11:373–385Google Scholar
  2. Bennasser Y, Bahraoui E (2002) HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-βII and -δ. FASEB J 16:546–554PubMedCrossRefGoogle Scholar
  3. Black PH (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 16:622–653PubMedCrossRefGoogle Scholar
  4. Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu B, Leeuwenburgh C (2009) Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18–30PubMedCentralPubMedCrossRefGoogle Scholar
  5. Cui XU, Dai Y, Wang SHL, Yamanaka H, Kobayashi K, Obata K, Chen J, Noguchi H (2008) Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia. Mol Pain. doi:10.1186/1744-8069-4-17 PubMedCentralPubMedGoogle Scholar
  6. Goldsmitha M, Avnia D, Ernst O, Glucksama Y, Rimlera G, Meijler B, Zora T (2009) Synergistic IL-10 induction by LPS and the ceramide-1-phosphate analog PCERA-1 is mediated by the cAMP and p38 MAP kinase pathways. Mol Immunol 46:1979–1987CrossRefGoogle Scholar
  7. Hackett TL, Holloway R, Holgate ST, Warner JA (2008) Dynamics of pro-inflammatory and anti-inflammatory cytokine release during acute inflammation in chronic obstructive pulmonary disease an ex vivo study. Respir Res 9:1–14CrossRefGoogle Scholar
  8. Hawrylowicz CM, O’Garra A (2005) Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 5:271–283PubMedCrossRefGoogle Scholar
  9. Inoue T, Boyle DL, Corr M, Hammaker D, Davis RJ, Flavell RA, Firestein GS (2006) Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38 activation in inflammatory arthritis. PNAS 103(14):5484–5489. doi:10.1073/pnas.0509188103 PubMedCrossRefGoogle Scholar
  10. Kanaan S, Poole S, Nayef ES, Suhayl J, Garabedian BS (1998) Interleukin-10 reduces the endotoxin-induced hyperalgesia in mice top of form. J Neuroimmunol 86:142–150PubMedCrossRefGoogle Scholar
  11. Kontoyiannis D, Kotlyarov A, Carballo E, Alexopoulou L, Blackshear PJ, Gaestel M, Davis R, Flavell R, Kollias G (2001) Interleukin-10 targets p38MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology. EMBO J 20:3760–3770PubMedCrossRefGoogle Scholar
  12. Kurien BT, Scofield RH (2006) Western blotting. Methods 38:283–293PubMedCrossRefGoogle Scholar
  13. Mace G, Miaczynshka M, Zerial M, Nebred AR (2005) Phosphorylation of EAA1 by P38MAPK regulates μ opioid receptor endocytosis. EMBO J 24:3235–3246PubMedCrossRefGoogle Scholar
  14. Möller B, Villiger PM (2006) Inhibition of IL-1, IL-6, and TNF-alpha in immune-mediated inflammatory diseases. J Immunopathol 27:391–408Google Scholar
  15. Rezazadeh SH, Zaringhalam J, Manaheji H, Kebryaeezadeh A (2009) Anti-inflammatory and anti-hyperalgesic activities of Stachys atho-recalyx extracts on CFA induced inflammation. J Med Plants Res 3:368–376Google Scholar
  16. Sabat R (2010) IL10 family of cytokines. Cytokine Growth Factor Rev 21:315–324PubMedCrossRefGoogle Scholar
  17. Samperio PM, Trejo A, Perez A (2008) Mycobacterium bovis Bacillus calmette-Gueria (BCG) stimulates IL10 production via the PI3K/AKT and P38MAPK pathway in human lung epithelial cells. Cell Immunol 251:37–42CrossRefGoogle Scholar
  18. Sandkühler J (2009) Models and mechanisms of hyperalgesia and allodynia. Am Physiol Soc 89:707–758Google Scholar
  19. Scott LD, Wolfe F, Huizinga WJ (2010) Rheumatoid arthritis. Lancet 376:1094–1108PubMedCrossRefGoogle Scholar
  20. Tekieh E, Zaringhalam J, Manaheji H, Maghsoudi A, Alani B, Zardooz H (2011) Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis. EXCLI J 10:23–33Google Scholar
  21. Winzen R, Kracht M, Ritter B, Wilhelm A, Chen CY, Shyu AB, Müller M, Gaestel M, Resch K, Holtmann H (1999) The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J 18:4969–4980PubMedCrossRefGoogle Scholar
  22. Zaringhalam J, Manaheji H, Mghsoodi N, Farokhi B, Mirzaiee V (2008) Spinal mu opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant-induced arthritis in rats. Clin Exp Pharmacol Physiol 10:1–7Google Scholar
  23. Zaringhalam J, Akbari A, Tekieh E, Manaheji H, Rezazadeh S (2010) Achillea santolina reduced serum IL-6 level and hyperalgesia during CFA-induced inflammation in male Wistar rats. J Chin Integr Med 12:1180–1189CrossRefGoogle Scholar
  24. Zarubin T, Han J (2005) Activation and signaling of the p38MAPK pathway. Cell Res 15:11–18PubMedCrossRefGoogle Scholar
  25. Zhang R, Wang L, Peng B (2008) Activation of p38 mitogen-activated protein kinase in rat periapical lesions. J Endod 34:1207–1210PubMedCrossRefGoogle Scholar
  26. Zimmermann M (1983) Ethical guidelines for investigations of experimental pain on conscious animals. Pain 16:109–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Jalal Zaringhalam
    • 1
    • 2
  • Zeinab Akhtari
    • 3
  • Akram Eidi
    • 3
  • Ali Haeri Ruhani
    • 3
  • Elaheh Tekieh
    • 2
  1. 1.Physiology DepartmentShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Neuroscience Research CentreShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran

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