Abstract
The objectives of this study were to observe the therapeutic effect of ozone (O3) of different concentrations on rat with rheumatoid arthritis (RA), and to investigate the role of O3 in regulating the level of TNF-α (tumor necrosis factor), TNF-R1 (tumor necrosis factor receptor 1), and TNF-R2. Forty-eight Wistar rats were randomly divided into eight groups. There are five O3 groups which were marked by 10, 20, 30, 40, and 50 μg/mL, respectively, control group, oxygen group, and RA model group. RA was induced in all rats by hypodermic injection of collagen II and complete Freund’s adjuvant except that in the control group. At 21 days after modeling, the rats in oxygen group were given an injection of oxygen in the knee joint weekly for 3 weeks, and the rats in O3 groups were injected the concentration of O3 as they marked weekly for 3 weeks. The thickness of hind paw, as well as the serum and synovial levels of TNF-α, TNF-R1, and TNF-R2 was observed. At the end of treatments, the thickness of the hind paws in O3-40 group is much less compared to RA group (P < 0.01). The serum levels of TNF-α, TNF-R1, and TNF-R2 showed no significant difference among all the groups (P > 0.05). However, the synovial levels of TNF-α and TNF-R2 in O3-40 and O3-50 groups are lower than those in RA group (P < 0.01). The synovial level of TNF-R1 in O3-40 group is higher than that in RA group (P < 0.05). In conclusion, intra-articular injection of O3 at 40 μg/mL can effectively suppress the joint swelling caused by RA. This mechanism is probably mediated by down-regulating synovial TNF-α and TNF-R2 and up-regulating TNF-R1 in the joint.
Similar content being viewed by others
References
Rhee DK, Marcelino J, Baker M et al (2005) The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest 115:622–631
Cassim B, Shaw OM, Mazur M et al (2009) Kallikreins, kininogens and kinin receptors on circulating and synovial fluid neutrophils: role in kinin generation in rheumatoid arthritis. Rheumatology (Oxford) 48:490–496
Ma MHY, Kingsley GH, Scott DL (2010) A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatology 49:91–98
Kawakami K, Ikari K, Kawamura K et al (2010) Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers: perioperative interruption of tumour necrosis factor-alpha blockers decreases complications. Rheumatology 49:341–347
Martinez-Sanchez G, Al-Dalain SM, Menendez S et al (2005) Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol 523:151–161
Cho H, Morgan D, Bauer A et al (2007) Signal transduction pathways of tumor necrosis factor-mediated lung injury induced by ozone in mice. Am J Resp Crit Care 175:829–836
Fakhrzadeh L, Laskin J, Laskin D (2004) Ozone-induced production of nitric oxide and TNF-{alpha} and tissue injury are dependent on NF-{kappa} B p50. AM J Physiol-Lung C 287:279–284
Hirose J, Tanaka S (2011) Animal models for bone and joint disease. CIA. CAIA Model Clin Calcium 21:253–259
Kastelein R, Hunter C, Cua D (2007) Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Immunology 25:221–229
Wilson N, Boniface K, Chan J et al (2007) Development, cytokine profile and function of human interleukin 17 producing helper T cells. Nat Immunol 8:950–957
Covacu R, Arvidsson L, Andersson A et al (2009) TLR activation induces TNF-alpha production from adult neural stem/progenitor cells. J Immunol 182(11):6889–6895
Venkatachalam K, Venkatesan B, Valente AJ et al (2009) WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-alpha (TNF-alpha)-stimulated cardiac fibroblast proliferation but inhibits TNF-alpha-induced cardiomyocyte death. J Biol Chem 284:14414–14427
Frey B, Gaipl US, Sarter K et al (2009) Whole body low dose irradiation improves the course of beginning polyarthritis in human TNF-transgenic mice. Autoimmunity 42:346–348
Cejka D, Hayer S, Niederreiter B et al (2010) Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis. Arthritis Rheum 62:2294–2302
Stanczyk J, Pedrioli D, Brentano F et al (2008) Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 58:1001–1009
Bowes J, Potter C, Gibbons L et al (2009) Investigation of genetic variants within candidate genes of the TNFRSF1B signalling pathway on the response to anti-TNF agents in a UK cohort of rheumatoid arthritis patients. Pharmacogenet Genom 19:319–327
Emery P, Keystone E, Tony H et al (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-TNF biologics: results from a 24-week multicentre randomised placebo controlled trial. Brit Med J 29:834–858
Feldmann M, Maini S (2008) Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev 223:7–19
Dey S, Snow D (2007) Cocaine exposure in vitro induces apoptosis in fetal locus coeruleus neurons through TNF-α-mediated induction of Bax and phosphorylated c-Jun NH2-terminal kinase. J Neurochem 103:542–556
Jain N, Sudhakar C, Swarup G (2007) Tumor necrosis factor–induced Caspase-1 gene expression: role of p73. FEBS J 274:4396–4407
Wang L, Du F, Wang X (2008) TNF-[alpha] induces two distinct caspase-8 activation pathways. Cell 133:693–703
Sikora J, Chlebna-Sokół D, Andrzejewska E et al (2008) Clinical evaluation of proinflammatory cytokine inhibitors (Stnfr I, sTNFR II, IL-1 ra), anti-inflammatory cytokines (IL-10, IL-13) and activation of neutrophils after burn-induced inflammation. Scand J Immunol 68:145–152
Oliveira J, Gupta S (2008) Disorders of apoptosis: mechanisms for autoimmunity in primary immunodeficiency diseases. J Clin Immunol 28:20–28
Pistilli E, Jackson J, Alway S (2006) Death receptor-associated pro-apoptotic signaling in aged skeletal muscle. Apoptosis 11:2115–2126
Acknowledgments
This study was supported by the grant of Natural Science Foundation of Guangdong Province (No. 8151051501000079).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, H., Yu, B., Lu, C. et al. The effect of intra-articular injection of different concentrations of ozone on the level of TNF-α, TNF-R1, and TNF-R2 in rats with rheumatoid arthritis. Rheumatol Int 33, 1223–1227 (2013). https://doi.org/10.1007/s00296-012-2529-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-012-2529-7