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. 2013 Apr;77(4):230-7.
doi: 10.1111/sji.12030.

IL-17 induces expression of vascular cell adhesion molecule through signalling pathway of NF-κB, but not Akt1 and TAK1 in vascular smooth muscle cells

H Zhang  1 , J Chen, X Liu, L Awar, A McMickle, F Bai, S Nagarajan, S Yu
Affiliations

IL-17 induces expression of vascular cell adhesion molecule through signalling pathway of NF-κB, but not Akt1 and TAK1 in vascular smooth muscle cells

H Zhang et al. Scand J Immunol. 2013 Apr.

Abstract

Interleukin-17 (IL-17) plays an important role in several autoimmune diseases. IL-17 can induce the expression of vascular cell adhesion molecule (VCAM-1) in aortic vascular smooth muscle cells (SMCs), which is important for the development of atherosclerosis. However, the signalling pathway of IL-17-induced VCAM-1 expression remains unclear. In this study, we reported that IL-17-induced expression of VCAM-1 in SMCs is dependent on NF-κB, but independent of Akt1 and TAK1. This is because knocking down Akt1 or TAK1 by siRNA did not reduce IL-17-induced activation of NF-κB and expression of VCAM-1, whereas knocking down NF-κB by siRNA markedly inhibited IL-17-mediated upregulation of VCAM-1 expression. In addition, IL-17-induced expression of VCAM-1 is partially dependent on activation of ERK1/2. Therefore, these signalling pathways of IL-17-mediated upregulation of VCAM-1 expression might be therapeutic targets for treatment of IL-17-mediated inflammation.

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Conflict of interest statement

Disclosures: The authors have no financial conflicts of interest.

Figures

Figure 1
Figure 1
IL-17 induces expression of VCAM-1 in SMCs. SMCs were treated with IL-17 (10–50ng/ml) for 12 hours. The VCAM-1 in whole cell extracts was identified by Western blots. Actin was used as equal loading. Western blots showed that IL-17 induces VCAM-1 expression (A), which is consistent with RT-PCR results that IL-17 promote VCAM-1 mRNA expression in SMCs (B). In addition, IL-17 is able to induce VCAM-1 expression in human aortic smooth muscle cells (C). The data is presented as the mean ± SE from three independent experiments. *, P < 0.05.
Figure 2
Figure 2
IL-17 induces expression of VCAM-1 in rat SMCs via activation of NF-kB. (A) The Rat SMCs were stimulated with IL-17 for different times. The whole cell lyses were blotted for phosphorylation of RelA and the degradation of cytoplasmic inhibitor IκBα. (B) NF-κB activity was determined by EMSA. The arrowhead indicated the band supershifted by antibody against Rel A. The probe sequence corresponds to the region between −116 and −79 upstream of transcriptional start site (+1) of Rat VCAM-1 gene. (C) The Rat SMCs were transfected with 7.5pmol/ml RELA or negative siRNA. After 2 days the cells were incubated with IL-17 (50 ng/ml) for 12 hours. Whole cell lyses was blotted with anti-RelA or anti-VCAM-1. The data presented as the mean ± SE from three independent experiments. *, P < 0.05 for the suppression of IL-17-induced VCAM-1 by RELA siRNA.
Figure 3
Figure 3
TRAF3 does not negatively regulate IL-17-mediated NF-κB activation and the expression of VCAM-1 in Rat SMCs. Rat SMCs transfected with 7.5pmol/ml negative control (neg), TRAF3, and TRAF6 siRNA were treated with or without IL-17 (50ng/ml) for different times (B) or 12 hours(A). Whole cell lyses were immunoblotted with anti-p-IκBα, anti-p-p65, anti-Traf3, anti-Traf6, anti-Gapdh (B) or anti-VCAM-1(A). Data are representative of five independent experiments. *, P < 0.05.
Figure 4
Figure 4
Knocking down TAK1 (MAP3K7) inhibits the phosphorylation of IκBα, but does not reduce the expression of VCAM-1 stimulated by IL-17 in Rat SMCs. The rat SMCs transfected with TAK1 siRNA (7.5pmol/ml) were treated with or without IL-17 for different times (B) or 12 hours (A). Whole cell lysates were immunoblotted with (A) anti-VCAM-1, (B) anti-TAK1, anti-p- IκBα, anti-p65 or Gapdh. The data are representative of three independent experiments.
Figure 5
Figure 5
IL-17 regulates VCAM-1 expression partially dependent on MAPK ERK1/2. The rested Rat SMCs were treated with inhibitor U0126 (25 µM) for 1 hour in advance and then incubated with or without IL17 for 15 min, 45 min (A) or 12 hours (B). Whole cell lyses were immunoblotted with anti-p-RelA, anti-IκBα, and anti-p-ERK1/2 (A) or with anti-VCAM-1 (B). *, P = 0.045.
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References

    1. Hemdan NY, Birkenmeier G, Wichmann G, et al. Interleukin-17-producing T helper cells in autoimmunity. Autoimmun. Rev. 2010;9:785–792. - PubMed
    1. Cua DJ, Tato CM. Innate IL-17-producing cells: The sentinels of the immune system. Nat. Rev. Immunol. 2010;10:479–489. - PubMed
    1. Iwakura Y, Ishigame H, SAijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity. 2011;34:149–158. - PubMed
    1. Park H, Li Z, Yang XO, et al. A distinct lineage of CD4+ T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 2005;6:1133–1141. - PMC - PubMed
    1. Lee YK, Turner H, Maynard CL, et al. Late developmental plasticity in the T helper 17 lineage. Immunity. 2009;30:92–107. - PMC - PubMed

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