Full Text:   <2736>

CLC number: R593.22

On-line Access: 2010-01-06

Received: 2010-03-08

Revision Accepted: 2010-07-02

Crosschecked: 2010-12-10

Cited: 6

Clicked: 5601

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.1 P.40-46


Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions

Author(s):  Wei-kun Hou, Lie-su Meng, Fang Zheng, Yu-rong Wen, Wen-hua Zhu, Cong-shan Jiang, Xiao-jing He, Yan Zhou, She-min Lu

Affiliation(s):  Department of Genetics and Molecular Biology, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an Jiaotong University, Xi’an 710061, China, Department of Dermatology and Venereology, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China, Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University, Xi’an 710061, China

Corresponding email(s):   shemin.lu@gmail.com

Key Words:  Methotrexate (MTX), Black seed oil (BSO), Pristane-induced arthritis (PIA), Interferon-γ, (IFN-γ, ), Interleukin-17A (IL-17A)

Wei-kun Hou, Lie-su Meng, Fang Zheng, Yu-rong Wen, Wen-hua Zhu, Cong-shan Jiang, Xiao-jing He, Yan Zhou, She-min Lu. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions[J]. Journal of Zhejiang University Science B, 2011, 12(1): 40-46.

@article{title="Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions",
author="Wei-kun Hou, Lie-su Meng, Fang Zheng, Yu-rong Wen, Wen-hua Zhu, Cong-shan Jiang, Xiao-jing He, Yan Zhou, She-min Lu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions
%A Wei-kun Hou
%A Lie-su Meng
%A Fang Zheng
%A Yu-rong Wen
%A Wen-hua Zhu
%A Cong-shan Jiang
%A Xiao-jing He
%A Yan Zhou
%A She-min Lu
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 1
%P 40-46
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000078

T1 - Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions
A1 - Wei-kun Hou
A1 - Lie-su Meng
A1 - Fang Zheng
A1 - Yu-rong Wen
A1 - Wen-hua Zhu
A1 - Cong-shan Jiang
A1 - Xiao-jing He
A1 - Yan Zhou
A1 - She-min Lu
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 1
SP - 40
EP - 46
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000078

Objective: This study was carried out to test the effects of )%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>methotrexate (MTX) and )%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>black seed oil (BSO) on )%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>pristane-induced arthritis (PIA) in rats. Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane, and then treated with MTX or BSO. Arthritis severity was evaluated macroscopically and microscopically. Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: The clinical arthritis severity was decreased after MTX treatment, while the BSO groups did not show significant changes compared with the disease group. The plasma NO level of the MTX group was significantly decreased compared with the disease group, but the BSO groups showed no difference from the disease group in plasma NO levels. The interferon-γ; (IFN-γ;) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group, but only showed a declining trend in the BSO groups compared with the disease group. Neither MTX nor BSO had an effect on the mRNA expressions of IL-4, transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α) in the spleen. Conclusions: MTX, but not BSO, can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abbas, A.T., Abdel-Aziz, M.M., Zalata, K.R., Al-Galel Tel, D.A., 2005. Effect of dexamethasone and Nigella sativa on peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model of allergic asthma. Egypt. J. Immunol., 12(1):95-102.

[2]Alarcón, G.S., 2000. Methotrexate use in rheumatoid arthritis. A clinician’s perspective. Immunopharmacology, 47(2-3):259-271.

[3]Bettelli, E., Korn, T., Oukka, M., Kuchroo, V.K., 2008. Induction and effector functions of TH17 cells. Nature, 453(7198):1051-1057.

[4]Budancamanak, M., Kanter, M., Demirel, A., Ocakci, A., Uysal, H., Karakaya, C., 2006. Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis. Arch. Toxicol., 80(11):768-776.

[5]Celtikci, B., Lawrance, A.K., Wu, Q., Rozen, R., 2009. Methotrexate-induced apoptosis is enhanced by altered expression of methylenetetrahydrofolate reductase. Anti-Cancer Drugs, 20(9):787-793.

[6]Cronstein, B.N., 2005. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol. Rev., 57(2):163-172.

[7]de Lathouder, S., Gerards, A.H., Dijkmans, B.A., Aarden, L.A., 2004. Two inhibitors of DNA-synthesis lead to inhibition of cytokine production via a different mechanism. Nucleosides Nucleotides Nucleic Acids, 23(8-9):1089-1100.

[8]Farrell, A.J., Blake, D.R., Palmer, R.M.J., Moncada, S., 1992. Increased concentrations of nitrite in synovial-fluid and serum samples suggest increased nitric-oxide synthesis in rheumatic diseases. Ann. Rheum. Dis., 51(11):1219-1222.

[9]Gerards, A.H., de Lathouder, S., de Groot, E.R., Dijkmans, B.A., Aarden, L.A., 2003. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology, 42(10):1189-1196.

[10]Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., Weaver, C.T., 2005. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol., 6(11):1123-1132.

[11]Helliwell, P.S., Hetthen, J., Sokoll, K., Green, M., Marchesoni, A., Lubrano, E., Veale, D., Emery, P., 2000. Joint symmetry in early and late rheumatoid and psoriatic arthritis: comparison with a mathematical model. Arthritis Rheum., 43(4):865-871.

[12]Herman, S., Zurgil, N., Langevitz, P., Ehrenfeld, M., Deutsch, M., 2008. Methotrexate selectively modulates TH1/TH2 balance in active rheumatoid arthritis patients. Clin. Exp. Rheumatol., 26(2):317-323.

[13]Holmberg, J., Tuncel, J., Yamada, H., Lu, S., Olofsson, P., Holmdahl, R., 2006. Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat. J. Immunol., 176(2):1172-1179.

[14]Ivanov, I.I., McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J., Cua, D.J., Littman, D.R., 2006. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell, 126(6):1121-1133.

[15]Klareskog, L., Padyukov, L., Ronnelid, J., Alfredsson, L., 2006. Genes, environment and immunity in the development of rheumatoid arthritis. Curr. Opin. Immunol., 18(6):650-655.

[16]Lange, F., Bajtner, E., Rintisch, C., Nandakumar, K.S., Sack, U., Holmdahl, R., 2005. Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis. Ann. Rheum. Dis., 64(4):599-605.

[17]Lee, D.M., Weinblatt, M.E., 2001. Rheumatoid arthritis. Lancet, 358(9285):903-911.

[18]Lu, S., Nordquist, N., Holmberg, J., Olofsson, P., Pettersson, U., Holmdahl, R., 2002. Both common and unique susceptibility genes in different rat strains with pristane-induced arthritis. Eur. J. Hum. Genet., 10(8):475-483.

[19]McLean-Tooke, A., Aldridge, C., Waugh, S., Spickett, G.P., Kay, L., 2009. Methotrexate, rheumatoid arthritis and infection risk—what is the evidence? Rheumatology, 48(8):867-871.

[20]Meng, L., Zhu, W., Jiang, C., He, X., Hou, W., Zheng, F., Holmdahl, R., Lu, S., 2010. Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats. Arthritis Res. Ther., 12(3):R103.

[21]Miranda-Carus, M.E., Balsa, A., Benito-Miguel, M., Perez de Ayala, C., Martin-Mola, E., 2004. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J. Immunol., 173(2):1463-1476.

[22]Mosmann, T.R., Coffman, R.L., 1989. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol., 7(1):145-173.

[23]Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., Cheroutre, H., 2007. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science, 317(5835):256-260.

[24]Olofsson, P., Holmdahl, R., 2007. Pristane-induced arthritis in the rat. Arthritis Res., 136(2):255-268.

[25]Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al., 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol., 6(11):1133-1141.

[26]Patiño-García, A., Zalacain, M., Marrodan, L., San-Julian, M., Sierrasesumaga, L., 2009. Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression. J. Pediatr., 154(5):688-693.

[27]Pratt, A.G., Isaacs, J.D., Mattey, D.L., 2009. Current concepts in the pathogenesis of early rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol., 23(1):37-48.

[28]Reddy, S.V.B., Wanchu, A., Khullar, M., Govindrajan, S., Bambery, P., 2005. Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis. Int. Immunopharmacol., 5(6):1085-1090.

[29]Romas, E., Sims, N.A., Hards, D.K., Lindsay, M., Quinn, J.W.M., Ryan, P.F.J., Dunstan, C.R., Martin, T.J., Gillespie, M.T., 2002. Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. Am. J. Pathol., 161(4):1419-1427.

[30]Salem, M.L., 2005. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol., 5(13-14):1749-1770.

[31]Savnik, A., Malmskov, H., Thomsen, H.S., Graff, L.B., Nielsen, H., Danneskiold-Samsoe, B., Boesen, J., Bliddal, H., 2001. Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory joint diseases. J. Rheumatol., 28(10):2193-2200.

[32]Seitz, M., Zwicker, M., Villiger, P.M., 2003. Pretreatment cytokine profiles of peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different American college of rheumatology response groups to methotrexate. J. Rheumatol., 30(1):28-35.

[33]Shahzad, M., Yang, X., Raza Asim, M.B., Sun, Q., Han, Y., Zhang, F., Cao, Y., Lu, S., 2009. Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats. Pulm. Pharmacol. Ther., 22(1):37-43.

[34]Shimura, C., Satoh, T., Takayama, K., Yokozeki, H., 2009. Methotrexate-related lymphoproliferative disorder with extensive vascular involvement in a patient with rheumatoid arthritis. J. Am. Acad. Dermatol., 61(1):126-129.

[35]Smolen, J.S., Aletaha, D., 2009. Developments in the clinical understanding of rheumatoid arthritis. Arthritis Res. Ther., 11(1):204.

[36]Tekeoglu, I., Dogan, A., Demiralp, L., 2006. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother. Res., 20(10):869-871.

[37]Wessels, J.A.M., Huizinga, T.W.J., Guchelaar, H.J., 2007. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology, 47(3):249-255.

[38]Yamamoto, T., 2009. Cutaneous manifestations associated with rheumatoid arthritis. Rheumatol. Int., 29(9):979-988.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE