Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide

Ryuki Shinohe, Masao Sato, Masao Takemura, Katsuji Shimizu, Hirohisa Koishi, Ryo Tanaka, Kuniaki Saito, Mitsuru Seishima

Research output: Contribution to journalArticle

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Abstract

Background: Anti-cytokine therapy is an effective therapy for rheumatoid arthritis. To know the kinetics of cytokine expression, we investigated mice with arthritis induced by anti-type II collagen monoclonal antibody (anti-CII Abs) plus lipopolysaccharide (LPS). Methods: BALB/c mice (7 weeks' age) were injected i.v. with anti-CII Abs 2 mg/mouse and 3 days later injected i.p. with 50 μ g of LPS. Mice developed arthritis, and the cytokine expressions in extracted legs were determined by RT-PCR. Serum cytokine concentrations were measured using ELISA. In addition, both sets of data were compared with those of TNF gene-deficient mice. Results: After induction of arthritis in wild-type mice, mRNA expression of TNF-α increased early, followed by IL-18. IL-1β and IL-6 mRNA expressions rose comparatively later. TNF-α, IL-1β and IL-6 concentrations in the serum reflected the level of their mRNA expressions. Interestingly, serum IL-18 level showed two distinct peaks, at early and later phase. In contrast, arthritis did not develop in TNF-α-deficient mice, and no elevation of IL-β or IL-6 in either serum or tissue mRNA was observed at any time point. Further, no increase in tissue mRNA levels was seen in TNF-α -deficient mice, however, there was a significant increase in serum IL-18 concentrations in the later phase. Conclusion: This study demonstrates that mRNA levels of TNF-α and IL-18 in both serum and joint tissue are increased, in the early phase with different patterns in mice with arthritis induced by anti-CII Abs plus LPS; IL-1β and IL-6 levels also increased in the later phase. The results using TNF-α -deficient mice indicate that TNF-α might play a crucial role as a key upstream molecule in the cytokine network of early inflammatory arthritis, and that TNF-α might trigger the synthesis of several other cytokines.

Original languageEnglish
Pages (from-to)53-62
Number of pages10
JournalJapanese Journal of Clinical Chemistry
Volume37
Issue number1
Publication statusPublished - 22-02-2008
Externally publishedYes

Fingerprint

Collagen Type II
Arthritis
Lipopolysaccharides
Interleukin-18
Monoclonal Antibodies
Cytokines
Messenger RNA
Interleukin-6
Interleukin-1
Tissue
Serum
Genes
Molecules
Kinetics
Rheumatoid Arthritis
Leg
Joints
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry

Cite this

Shinohe, R., Sato, M., Takemura, M., Shimizu, K., Koishi, H., Tanaka, R., ... Seishima, M. (2008). Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide. Japanese Journal of Clinical Chemistry, 37(1), 53-62.
Shinohe, Ryuki ; Sato, Masao ; Takemura, Masao ; Shimizu, Katsuji ; Koishi, Hirohisa ; Tanaka, Ryo ; Saito, Kuniaki ; Seishima, Mitsuru. / Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide. In: Japanese Journal of Clinical Chemistry. 2008 ; Vol. 37, No. 1. pp. 53-62.
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abstract = "Background: Anti-cytokine therapy is an effective therapy for rheumatoid arthritis. To know the kinetics of cytokine expression, we investigated mice with arthritis induced by anti-type II collagen monoclonal antibody (anti-CII Abs) plus lipopolysaccharide (LPS). Methods: BALB/c mice (7 weeks' age) were injected i.v. with anti-CII Abs 2 mg/mouse and 3 days later injected i.p. with 50 μ g of LPS. Mice developed arthritis, and the cytokine expressions in extracted legs were determined by RT-PCR. Serum cytokine concentrations were measured using ELISA. In addition, both sets of data were compared with those of TNF gene-deficient mice. Results: After induction of arthritis in wild-type mice, mRNA expression of TNF-α increased early, followed by IL-18. IL-1β and IL-6 mRNA expressions rose comparatively later. TNF-α, IL-1β and IL-6 concentrations in the serum reflected the level of their mRNA expressions. Interestingly, serum IL-18 level showed two distinct peaks, at early and later phase. In contrast, arthritis did not develop in TNF-α-deficient mice, and no elevation of IL-β or IL-6 in either serum or tissue mRNA was observed at any time point. Further, no increase in tissue mRNA levels was seen in TNF-α -deficient mice, however, there was a significant increase in serum IL-18 concentrations in the later phase. Conclusion: This study demonstrates that mRNA levels of TNF-α and IL-18 in both serum and joint tissue are increased, in the early phase with different patterns in mice with arthritis induced by anti-CII Abs plus LPS; IL-1β and IL-6 levels also increased in the later phase. The results using TNF-α -deficient mice indicate that TNF-α might play a crucial role as a key upstream molecule in the cytokine network of early inflammatory arthritis, and that TNF-α might trigger the synthesis of several other cytokines.",
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Shinohe, R, Sato, M, Takemura, M, Shimizu, K, Koishi, H, Tanaka, R, Saito, K & Seishima, M 2008, 'Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide', Japanese Journal of Clinical Chemistry, vol. 37, no. 1, pp. 53-62.

Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide. / Shinohe, Ryuki; Sato, Masao; Takemura, Masao; Shimizu, Katsuji; Koishi, Hirohisa; Tanaka, Ryo; Saito, Kuniaki; Seishima, Mitsuru.

In: Japanese Journal of Clinical Chemistry, Vol. 37, No. 1, 22.02.2008, p. 53-62.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cytokine profiles in mice with arthritis induced by anti-type II collagen monoclonal antibody plus lipopolysaccharide

AU - Shinohe, Ryuki

AU - Sato, Masao

AU - Takemura, Masao

AU - Shimizu, Katsuji

AU - Koishi, Hirohisa

AU - Tanaka, Ryo

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

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Y1 - 2008/2/22

N2 - Background: Anti-cytokine therapy is an effective therapy for rheumatoid arthritis. To know the kinetics of cytokine expression, we investigated mice with arthritis induced by anti-type II collagen monoclonal antibody (anti-CII Abs) plus lipopolysaccharide (LPS). Methods: BALB/c mice (7 weeks' age) were injected i.v. with anti-CII Abs 2 mg/mouse and 3 days later injected i.p. with 50 μ g of LPS. Mice developed arthritis, and the cytokine expressions in extracted legs were determined by RT-PCR. Serum cytokine concentrations were measured using ELISA. In addition, both sets of data were compared with those of TNF gene-deficient mice. Results: After induction of arthritis in wild-type mice, mRNA expression of TNF-α increased early, followed by IL-18. IL-1β and IL-6 mRNA expressions rose comparatively later. TNF-α, IL-1β and IL-6 concentrations in the serum reflected the level of their mRNA expressions. Interestingly, serum IL-18 level showed two distinct peaks, at early and later phase. In contrast, arthritis did not develop in TNF-α-deficient mice, and no elevation of IL-β or IL-6 in either serum or tissue mRNA was observed at any time point. Further, no increase in tissue mRNA levels was seen in TNF-α -deficient mice, however, there was a significant increase in serum IL-18 concentrations in the later phase. Conclusion: This study demonstrates that mRNA levels of TNF-α and IL-18 in both serum and joint tissue are increased, in the early phase with different patterns in mice with arthritis induced by anti-CII Abs plus LPS; IL-1β and IL-6 levels also increased in the later phase. The results using TNF-α -deficient mice indicate that TNF-α might play a crucial role as a key upstream molecule in the cytokine network of early inflammatory arthritis, and that TNF-α might trigger the synthesis of several other cytokines.

AB - Background: Anti-cytokine therapy is an effective therapy for rheumatoid arthritis. To know the kinetics of cytokine expression, we investigated mice with arthritis induced by anti-type II collagen monoclonal antibody (anti-CII Abs) plus lipopolysaccharide (LPS). Methods: BALB/c mice (7 weeks' age) were injected i.v. with anti-CII Abs 2 mg/mouse and 3 days later injected i.p. with 50 μ g of LPS. Mice developed arthritis, and the cytokine expressions in extracted legs were determined by RT-PCR. Serum cytokine concentrations were measured using ELISA. In addition, both sets of data were compared with those of TNF gene-deficient mice. Results: After induction of arthritis in wild-type mice, mRNA expression of TNF-α increased early, followed by IL-18. IL-1β and IL-6 mRNA expressions rose comparatively later. TNF-α, IL-1β and IL-6 concentrations in the serum reflected the level of their mRNA expressions. Interestingly, serum IL-18 level showed two distinct peaks, at early and later phase. In contrast, arthritis did not develop in TNF-α-deficient mice, and no elevation of IL-β or IL-6 in either serum or tissue mRNA was observed at any time point. Further, no increase in tissue mRNA levels was seen in TNF-α -deficient mice, however, there was a significant increase in serum IL-18 concentrations in the later phase. Conclusion: This study demonstrates that mRNA levels of TNF-α and IL-18 in both serum and joint tissue are increased, in the early phase with different patterns in mice with arthritis induced by anti-CII Abs plus LPS; IL-1β and IL-6 levels also increased in the later phase. The results using TNF-α -deficient mice indicate that TNF-α might play a crucial role as a key upstream molecule in the cytokine network of early inflammatory arthritis, and that TNF-α might trigger the synthesis of several other cytokines.

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