July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Apigenin Inhibits LPS-induced Microglia Activation by Modulating MicroRNA Expression
Author Affiliations & Notes
  • Onuma Chumsakul
    Rohto Pharmaceutical Co., Ltd, Kizugawa, Kyoto, Japan
  • Yoshihiro Takai
    Rohto Pharmaceutical Co., Ltd, Kizugawa, Kyoto, Japan
  • Takahiro Kurose
    Rohto Pharmaceutical Co., Ltd, Kizugawa, Kyoto, Japan
  • Yoichi Honma
    Rohto Pharmaceutical Co., Ltd, Kizugawa, Kyoto, Japan
  • Footnotes
    Commercial Relationships   Onuma Chumsakul, Rohto Pharmaceutical Co., Ltd (E); Yoshihiro Takai, Rohto Pharmaceutical Co., Ltd (E); Takahiro Kurose, Rohto Pharmaceutical Co., Ltd (E); Yoichi Honma, Rohto Pharmaceutical Co., Ltd (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3998. doi:
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      Onuma Chumsakul, Yoshihiro Takai, Takahiro Kurose, Yoichi Honma; Apigenin Inhibits LPS-induced Microglia Activation by Modulating MicroRNA Expression. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3998.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Several studies report a role for apigenin in inhibiting microglia activation; however, the molecular mechanism associated with this activity remains unknown. Here, we examined apigenin-mediated inhibition of the expression of proinflammatory genes in activated microglia by analyzing microRNAs (miRNAs), particularly miR-155, which regulate inflammatory cytokines and thereby contribute to microglia-activation phenotypes. Additionally, we investigated the role of Ets2, a transcriptional activator of primary miR-155 (pri-miR-155).

Methods : The microglia cell line BV2 was incubated with various concentrations of apigenin for 2 h prior to lipopolysaccharide (LPS) stimulation, followed by collection at 24 h and assessment of the expression of proinflammatory genes [interleukin-1β (il1b), C-C motif chemokine ligand 2 (ccl2), C-X-C motif chemokine 10 (cxcl10), tumor necrosis factor-α, and colony stimulating factor 1 (csf1)] and miRNAs (miR-155, miR-125b, and miR-146a). Similar experiments were undertaken to determine the effect of apigenin on Ets2 and pri-miR-155 levels at various time points following LPS stimulation.

Results : Apigenin at 10 µM strongly suppressed il1b, ccl2, cxcl10, and csf1 by 6.7-, 3.6-, 9.1-, and 2.4-fold, respectively, relative to levels observed following treatment with LPS alone, with these suppressive effects occurring in a concentration-dependent manner. Additionally, analysis of miR-155, miR-125b, and miR-146a revealed that apigenin treatment attenuated their expression by 2.9-, 2.0-, and 1.8-fold, respectively. Moreover, Ets2 levels were attenuated 1.5-3.7 fold by apigenin treatment at early time points (from 3-6 h), followed by a decline in this effect over time, whereas pri-miR-155 levels were suppressed from 6 h by 2.1 fold, with this effect lasting up to 24 h (1.7 fold).

Conclusions : These results demonstrate that apigenin inhibited proinflammatory cytokine expression by regulating multiple miRNAs and represent the first findings suggesting that apigenin modulates miR-155 through the Ets2 pathway. Further investigations are required to elucidate the apigenin-specific molecular mechanism in order to promote its development for microglia-targeted treatment or prevention of retinal degenerative diseases.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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