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IL-6/sIL-6R trans-signalling, but not TNF-α induced angiogenesis in a HUVEC and synovial cell co-culture system

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Abstract

Angiogenesis in synovia is a characteristic of RA patients. We examined whether IL-6 or TNF-α induce tubule formation in a co-culture system of fibroblast-like synovial cells from RA patients (RA-FLS) and human umbilical vein endothelial cells (HUVEC). The effects of IL-6 and TNF-α on the expression of angiogenic factors in RA-FLS and HUVEC, and the proliferation of HUVEC were also studied. IL-6 + sIL-6R induced tubule formation, whereas IL-6 alone did not. IL-6/sIL-6R-induced tubule formation was completely suppressed by the addition of either anti-IL-6R or anti-VEGF antibody. TNF-α did not induce tubule formation. On the contrary, it decreased CD31-positive area compared with the control. IL-6 + sIL-6R augmented VEGF production in RA-FLS, whereas IL-6 alone did not. Anti-IL-6R antibody suppressed IL-6/sIL-6R-induced VEGF production, but not spontaneous VEGF production. In contrast, TNF-α did not induce VEGF production from RA-FLS and HUVEC. IL-6 + sIL-6R stimulation of RA-FLS strongly induced mRNA expression of VEGF, but not of other angiogenic factors, such as EGF, bFGF, TGF-β, IL-1, TNF-α and IL-8. Neither IL-6 nor IL-6/sIL-6R promoted HUVEC proliferation, whereas TNF-α significantly inhibited VEGF-induced HUVEC proliferation. In conclusion, IL-6/sIL-6R complex showed angiogenic activity via the production of VEGF from RA-FLS, but TNF-α was anti-angiogenic in our experimental system.

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Authors and Affiliations

  1. Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan

    Misato Hashizume, Naohiko Hayakawa, Miho Suzuki & Masahiko Mihara

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  1. Misato Hashizume
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  2. Naohiko Hayakawa
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  3. Miho Suzuki
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  4. Masahiko Mihara
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Correspondence to Masahiko Mihara.

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Hashizume, M., Hayakawa, N., Suzuki, M. et al. IL-6/sIL-6R trans-signalling, but not TNF-α induced angiogenesis in a HUVEC and synovial cell co-culture system. Rheumatol Int 29, 1449–1454 (2009). https://doi.org/10.1007/s00296-009-0885-8

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