Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family

Mihara, Masahiko; Kasutani, Keiko; Okazaki, Makoto; Nakamura, Akira; Kawai, Shigeto; Sugimoto, Masamichi; Matsumoto, Yoshihiro; Ohsugi, Yoshiyuki

doi:10.1016/j.intimp.2005.05.010

Cited by 295 publications

(193 citation statements)

References 14 publications

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“…Its molecular weight is ~ 150 Kd [24] and it binds to sIL-6R in a dose-dependent manner and saturates the receptor at ~ 0.1µg/ml. It also competitively inhibits IL-6 binding to sIL-6R, with complete inhibition seen at ~ 4µg/ml [10].…”

Section: Tocilizumab and Other Il-6 Agents Currently Under Developmentmentioning

confidence: 97%

“…IL-6 can activate cells through 2 signalling pathways; the first is the membrane-bound (mIL-6R) via activation of glycoprotein 130 and the second is via proteolytic cleavage of the mIL-6R that leads to the generation of a soluble receptor for IL-6 (sIL-6R) [8,9]. The binding of IL-6 to sIL-6R enables the stimulation of cells that lack endogenous soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine [10,11].…”

Section: The Role Of Interleukin-6 In the Pathogenesis Of Rheumatoid mentioning

confidence: 99%

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Targeting Interleukin-6 in Rheumatoid Arthritis

Yusof

Emery

2013

Drugs

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Section: Tocilizumab and Other Il-6 Agents Currently Under Developmentmentioning

confidence: 97%

Section: The Role Of Interleukin-6 In the Pathogenesis Of Rheumatoid mentioning

confidence: 99%

Targeting Interleukin-6 in Rheumatoid Arthritis

Yusof

Emery

2013

Drugs

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“…Tocilizumab is a humanized anti-human IL-6R antibody and binds to the IL-6-binding site of human IL-6R. It is known to competitively inhibit IL-6/IL-6R signaling and completely neutralizes IL-6 activities (15,16). A series of clinical studies has successfully shown that the suppression of IL-6/IL-6R signaling by tocilizumab is therapeutically effective in alleviating Castleman's disease and rheumatoid arthritis (17,18).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells

et al. 2016

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Abstract. Ovarian cancer is a leading cause of malignant gynecological tumor-related mortality among women. The treatment of ovarian cancer patients continues to be challenging. MicroRNA-106a (miR-106a) is widely expressed in diverse human tumors. In the present study, we investigated the biological and pathological roles of miR-106a in ovarian cancers. We found that miR-106a expression was significantly increased in primary ovarian cancer tissues and ovarian cancer cells compared with the level in normal tissues. Ectopic expression of an miR-106a inhibitor attenuated ovarian cancer cell proliferation and invasion. miR-106a promoted the growth and invasion of SKOV3 cells by targeting phosphatase and tensin homolog (PTEN). Furthermore, the present study revealed that IL-6 inhibited miR-106a expression by activating STAT3. Tocilizumab, a humanized anti-human IL-6R antibody, that competitively inhibits IL-6/IL-6R signaling, did not inhibit the proliferation and invasion of SKOV3 cells. In conclusion, our studies revealed that miR-106a was significantly increased in the ovarian cancer tissues and cell lines. Downregulation of the expression of miR-106a inhibited cell growth and metastasis of ovarian cancer cells. Together, the present study suggests that miR-106a acts as an oncogene in ovarian cancers.

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“…Tocilizumab (TCZ) is a monoclonal anti-interleukin-6 (IL-6) receptor antibody that binds to cell membrane-bound IL-6 receptors and to free soluble IL-6 receptors in the serum, thereby blocking IL-6 signalling into cells [1]. This drug was developed to treat patients with rheumatoid arthritis (RA), Castleman’s disease and juvenile idiopathic arthritis, and has been approved as a treatment for these indications in Japan [2–9].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

Nishimoto

Takagi²

2010

Mod Rheumatol

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As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.

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Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family

Cited by 295 publications

References 14 publications

Targeting Interleukin-6 in Rheumatoid Arthritis

Targeting Interleukin-6 in Rheumatoid Arthritis

MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

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