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
- 188 Downloads
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.
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.
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.
KeywordsIL10 Arthritis Hyperalgesia Mu opioid receptor p38MAPK
This project was supported by Iran National Science Foundation (INSF) and Neuroscience Research Centre of Shahid Beheshti University of Medical Sciences.
- 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
- 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
- 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
- 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
- Sandkühler J (2009) Models and mechanisms of hyperalgesia and allodynia. Am Physiol Soc 89:707–758Google Scholar
- 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
- 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
- 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