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Article

Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells

  • Authors:
    • Nuerbiyemu Mijiti
    • Akimasa Someya
    • Isao Nagaoka
  • View Affiliations / Copyright

    Affiliations: Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo 113‑8421, Japan
  • Article Number: 1300
    |
    Published online on: September 16, 2021
       https://doi.org/10.3892/etm.2021.10735
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Abstract

The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL‑6 and IL‑8) by IL‑1β‑stimulated synovial cells. Synovial MH7A cells were stimulated with IL‑1β in the absence or presence of isoflavone derivatives, and IL‑6 and IL‑8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL‑6, but not IL‑8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL‑6 or IL‑8 by IL‑1β‑stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein‑mediated inhibition of IL‑6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF‑κB p65, ERK1/2 and p38 MAPK. Daidzein significantly inhibited the phosphorylation of NF‑κB p65 and ERK1/2, but not p38 MAPK in IL‑1β‑stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL‑6, but not IL‑8, by IL‑1β‑stimulated synovial MH7A cells via the suppression of NF‑κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti‑inflammatory effects via the inhibition of IL‑6 production.
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1 

Huber LC, Distler O, Tarner I, Gay RE, Gay S and Pap T: Synovial fibroblasts: Key players in rheumatoid arthritis. Rheumatol (Oxford). 45:669–675. 2006.PubMed/NCBI View Article : Google Scholar

2 

Mathiessen A and Conaghan PG: Synovitis in osteoarthritis: Current understanding with therapeutic implications. Arthritis Res Ther. 19(18)2017.PubMed/NCBI View Article : Google Scholar

3 

Storch H, Zimmermann B, Resch B, Tykocinski LO, Moradi B, Horn P, Kaya Z, Blank N, Rehart S, Thomsen M, et al: Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return. Ann Rheum Dis. 75:924–32. 2016.PubMed/NCBI View Article : Google Scholar

4 

Wojdasiewicz P, Poniatowski ŁA and Szukiewicz D: The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014(561459)2014.PubMed/NCBI View Article : Google Scholar

5 

Pelletier JP, Martel-Pelletier J and Abramson SB: Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets. Arthritis Rheum. 44:1237–1247. 2001.PubMed/NCBI View Article : Google Scholar

6 

Malemud CJ: Biologic basis of osteoarthritis: State of the evidence. Curr Opin Rheumatol. 27:289–294. 2015.PubMed/NCBI View Article : Google Scholar

7 

Barnes S, Prasain J, D'Alessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle E and Weaver CM: The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct. 2:235–244. 2011.PubMed/NCBI View Article : Google Scholar

8 

Barnes S: The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphat Res Biol. 8:89–98. 2010.PubMed/NCBI View Article : Google Scholar

9 

Beck V, Rohr U and Jungbauer A: Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy? J Steroid Biochem Mol Biol. 94:499–518. 2005.PubMed/NCBI View Article : Google Scholar

10 

Munro IC, Harwood M, Hlywka JJ, Stephen AM, Doull J, Flamm WG and Adlercreutz H: Soy isoflavones: A safety review. Nutr Rev. 61:1–33. 2003.PubMed/NCBI View Article : Google Scholar

11 

Vitale DC, Piazza C, Melilli B, Drago F and Salomone S: Isoflavones: Estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet. 38:15–25. 2013.PubMed/NCBI View Article : Google Scholar

12 

Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, Ogawa S, Inoue S, Muramatsu M and Masamune Y: Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull. 24:351–356. 2001.PubMed/NCBI View Article : Google Scholar

13 

Rodriguez-Roque MJ, Rojas-Grau MA, Elez-Martinez P and Martin-Belloso O: Soymilk phenolic compounds, isoflavones and antioxidant activity as affected by in vitro gastrointestinal digestion. Food Chem. 136:206–212. 2013.PubMed/NCBI View Article : Google Scholar

14 

Chacko BK, Chandler RT, D'Alessandro TL, Mundhekar A, Khoo NK, Botting N, Barnes S and Patel PP: Anti-inflammatory effects of isoflavones are dependent on flow and human endothelial cell PPARgamma. J Nutr. 137:351–356. 2007.PubMed/NCBI View Article : Google Scholar

15 

Hong H, Landauer MR, Foriska MA and Ledney GD: Antibacterial activity of the soy isoflavone genistein. J Basic Microbiol. 46:329–335. 2006.PubMed/NCBI View Article : Google Scholar

16 

Kang JL, Lee HW, Lee HS, Pack IS, Chong Y, Castranova V and Koh Y: Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Respir Crit Care Med. 164:2206–2212. 2001.PubMed/NCBI View Article : Google Scholar

17 

Verdrengh M, Jonsson IM, Holmdahl R and Tarkowski A: Genistein as an anti-inflammatory agent. Inflamm Res. 52:341–346. 2003.PubMed/NCBI View Article : Google Scholar

18 

Hooshmand S, Soung do Y, Lucas EA, Madihally SV, Levenson CW and Arjmandi BH: Genistein reduces the production of proinflammatory molecules in human chondrocytes. J Nutr Biochem. 18:609–614. 2007.PubMed/NCBI View Article : Google Scholar

19 

Li J, Li J, Yue Y, Hu Y, Cheng W, Liu R, Pan X and Zhang P: Genistein suppresses tumor necrosis factor alpha-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells. Drug Des Devel Ther. 8:315–323. 2014.PubMed/NCBI View Article : Google Scholar

20 

Choi EY, Jin JY, Lee JY, Choi JI, Choi IS and Kim SJ: Anti-inflammatory effects and the underlying mechanisms of action of daidzein in murine macrophages stimulated with Prevotella intermedia lipopolysaccharide. J Periodontal Res. 47:204–211. 2012.PubMed/NCBI View Article : Google Scholar

21 

Sheu F, Lai HH and Yen GC: Suppression effect of soy isoflavones on nitric oxide production in RAW 264.7 macrophages. J Agric Food Chem. 49:1767–1772. 2001.PubMed/NCBI View Article : Google Scholar

22 

Yamagishi Y, Someya A, Imai K, Nagao J and Nagaoka I: Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells. Mol Med Rep. 16:1353–1359. 2017.PubMed/NCBI View Article : Google Scholar

23 

Yamagishi Y, Someya A and Nagaoka I: Citrulline cooperatively exerts an anti-inflammatory effect on synovial cells with glucosamine and N-acetylglucosamine. Biomed Rep. 13:37–42. 2020.PubMed/NCBI View Article : Google Scholar

24 

Someya A, Ikegami T, Sakamoto K and Nagaoka I: Glucosamine downregulates the IL-1beta-induced expression of proinflammatory cytokine genes in human synovial MH7A cells by O-GlcNAc modification-dependent and -independent mechanisms. PLoS One. 11(e0165158)2016.PubMed/NCBI View Article : Google Scholar

25 

Barnes PJ and Karin M: Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 336:1066–1071. 1997.PubMed/NCBI View Article : Google Scholar

26 

Kyriakis JM and Avruch J: Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol Rev. 92:689–737. 2012.PubMed/NCBI View Article : Google Scholar

27 

Tak PP and Firestein GS: NF-kappaB: A key role in inflammatory diseases. J Clin Invest. 107:7–11. 2001.PubMed/NCBI View Article : Google Scholar

28 

Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E: Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007(45673)2007.PubMed/NCBI View Article : Google Scholar

29 

Weber A, Wasiliew P and Kracht M: Interleukin-1 (IL-1) pathway. Sci Signal. 3(cm1)2010.PubMed/NCBI View Article : Google Scholar

30 

Kawai T and Akira S: TLR signaling. Semin Immunol. 19:24–32. 2007.PubMed/NCBI View Article : Google Scholar

31 

Zandi E and Karin M: Bridging the gap: Composition, regulation, and physiological function of the IkappaB kinase complex. Mol Cell Biol. 19:4547–4551. 1999.PubMed/NCBI View Article : Google Scholar

32 

Zandi E, Chen Y and Karin M: Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: Discrimination between free and NF-kappaB-bound substrate. Science. 281:1360–1363. 1998.PubMed/NCBI View Article : Google Scholar

33 

Sabio G and Davis RJ: TNF and MAP kinase signalling pathways. Semin Immunol. 26:237–245. 2014.PubMed/NCBI View Article : Google Scholar

34 

Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B and Pope RM: Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: The dominant role for NF-kappa B but not C/EBP beta or c-Jun. J Immunol. 165:7199–7206. 2000.PubMed/NCBI View Article : Google Scholar

35 

Saccani S, Pantano S and Natoli G: p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immunol. 3:69–75. 2002.PubMed/NCBI View Article : Google Scholar

36 

Hoffmann E, Dittrich-Breiholz O, Holtmann H and Kracht M: Multiple control of interleukin-8 gene expression. J Leukoc Biol. 72:847–855. 2002.PubMed/NCBI

37 

Hoffmann E, Thiefes A, Buhrow D, Dittrich-Breiholz O, Schneider H, Resch K and Kracht M: MEK1-dependent delayed expression of Fos-related antigen-1 counteracts c-Fos and p65 NF-kappaB-mediated interleukin-8 transcription in response to cytokines or growth factors. J Biol Chem. 280:9706–9718. 2005.PubMed/NCBI View Article : Google Scholar

38 

Srirangan S and Choy EH: The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2:247–56. 2010.PubMed/NCBI View Article : Google Scholar

39 

Takahashi A, de Andres MC, Hashimoto K, Itoi E and Oreffo RO: Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthritis Cartilage. 23:1946–1954. 2015.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Mijiti N, Someya A and Nagaoka I: Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells. Exp Ther Med 22: 1300, 2021.
APA
Mijiti, N., Someya, A., & Nagaoka, I. (2021). Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells. Experimental and Therapeutic Medicine, 22, 1300. https://doi.org/10.3892/etm.2021.10735
MLA
Mijiti, N., Someya, A., Nagaoka, I."Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells". Experimental and Therapeutic Medicine 22.5 (2021): 1300.
Chicago
Mijiti, N., Someya, A., Nagaoka, I."Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1300. https://doi.org/10.3892/etm.2021.10735
Copy and paste a formatted citation
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Spandidos Publications style
Mijiti N, Someya A and Nagaoka I: Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells. Exp Ther Med 22: 1300, 2021.
APA
Mijiti, N., Someya, A., & Nagaoka, I. (2021). Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells. Experimental and Therapeutic Medicine, 22, 1300. https://doi.org/10.3892/etm.2021.10735
MLA
Mijiti, N., Someya, A., Nagaoka, I."Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells". Experimental and Therapeutic Medicine 22.5 (2021): 1300.
Chicago
Mijiti, N., Someya, A., Nagaoka, I."Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1300. https://doi.org/10.3892/etm.2021.10735
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