Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The protective effect of berberine on Propionibacterium acnes-induced inflammatory response in human monocytes

여드름균에 의해 염증 반응이 유도된 인간 단핵구 세포에서 알칼로이드 화합물 berberine의 항염증 효과

  • Received : 2018.04.11
  • Accepted : 2018.05.23
  • Published : 2018.06.30
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Abstract

In this study, we investigated the anti-inflammatory activity of berberine using human monocytes. Infection of Propionibacterium acnes induced the production of nitric oxide (NO) and the pro-inflammatory cytokines such as, $TNF-{\alpha}$, IL-8 and $IL-1{\beta}$ in THP-1 monocytic cells. However, when berberine was supplemented in these P. acnes-induced THP-1 cells, the production of pro-inflammatory cytokines and NO was significantly reduced. We also analyzed signaling pathways of the antiinflammatory function of berberine and found that berberine suppressed the phosphorylation of ERK1/2, JNK and p38 and the expression and nuclear translocation of $NF-{\kappa}B$ p65 in the P. acnes-induced cells. From these results, we concluded that berberine can effectively exert the anti-inflammatory activity via suppressing the $NF-{\kappa}B$ and mitogen-activated protein kinases signaling pathways in human monocytes. Moreover, these results suggest the feasibility of developing natural therapeutics using berberine for the treatment of P. acnes-induced inflammatory diseases.

본 연구에서는 인간 단핵구 세포인 THP-1 세포를 이용하여 berberine의 항염증 활성을 조사 하였다. Propionibacterium acnes의 감염은 THP-1 세포에서 산화질소(NO)와 $TNF-{\alpha}$, IL-8 및 $IL-1{\beta}$와 같은 전 염증성 사이토카인의 생산을 유도했다. 그러나, P. acnes에 의해 유도된 THP-1 세포에 berberine을 처리했을 때, 전 염증성 사이토카인 및 NO의 생성이 유의하게 감소하였다. 또한 우리는 berberine의 항 염증 기능의 신호 전달 경로를 분석하여 berberine이 P. acnes 유도 세포에서 ERK1/2, JNK 및 p38의 인산화를 억제하고 $NF-{\kappa}B$ p65의 발현 및 핵이동을 억제한다는 것을 발견했다. 이러한 결과로부터 berberine은 인간 단핵구 세포에서 $NF-{\kappa}B$ 및 MAPK 신호 전달 경로를 억제함으로써 항 염증 활성을 효과적으로 발휘할 수 있다고 결론지었다. 또한, 이러한 결과는 P. acnes에 의해 유발된 염증성 질환의 치료를 위해 천연물 소재에서 유래한 알칼로이드 화합물인 berberine을 사용하여 천연 치료제를 개발할 수 있는 가능성을 제시하였다.

Keywords

References

  1. Wang YY, Ryu AR, Jin S, Jeon YM, Lee MY (2017) Chlorin e6-mediated photodynamic therapy suppresses P. acnes-induced inflammatory response via $NF{\kappa}B$ and MAPKs signaling pathway. PLoS One 12: e0170599 https://doi.org/10.1371/journal.pone.0170599
  2. Omer H, McDowell A, Alexeyev OA (2017) Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies. Clin Dermatol 35: 118-129 https://doi.org/10.1016/j.clindermatol.2016.10.003
  3. Suh DH, Kwon HH (2015) What's new in the physiopathology of acne? Br J Dermatol 172 Suppl 1: 13-19
  4. Suh DH (2010) Pharmacologic treatment of acne. J Kor Med Assoc 53: 623-629 https://doi.org/10.5124/jkma.2010.53.7.623
  5. Dessinioti C, Katsambas AD (2010) The role of Propionibacterium acnes in acne pathogenesis: facts and controversies. Clin Dermatol 28: 2-7 https://doi.org/10.1016/j.clindermatol.2009.03.012
  6. Thiboutot DM, Layton AM, Eady EA (2014) IL-17: a key player in the P. acnes inflammatory cascade? J Invest Dermatol 134: 307-310 https://doi.org/10.1038/jid.2013.400
  7. Farrar MD, Ingham E (2004) Acne: inflammation. Clin Dermatol 22: 380-384 https://doi.org/10.1016/j.clindermatol.2004.03.006
  8. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL (2002) Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 169: 1535-1541 https://doi.org/10.4049/jimmunol.169.3.1535
  9. Jugeau S, Tenaud I, Knol AC, Jarrousse V, Quereux G, Khammari A, Dreno B (2005) Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol 153: 1105-1113 https://doi.org/10.1111/j.1365-2133.2005.06933.x
  10. Grange PA, Raingeaud J, Calvez V, Dupin N (2009) Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the $NF-{\kappa}B$ and MAPK pathways. J Dermatol Sci 56: 106-112 https://doi.org/10.1016/j.jdermsci.2009.08.001
  11. Zou K, Li Z, Zhang Y, Zhang HY, Li B, Zhu WL, Shi JY, Jia Q, Li YM (2017) Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol Sin 38: 157-167 https://doi.org/10.1038/aps.2016.125
  12. Li JY, Wang XB, Luo JG, Kong LY (2015) Seasonal variation of alkaloid contents and anti-Inflammatory activity of Rhizoma coptidis based on fingerprints combined with chemometrics methods. J Chromatogr Sci 53: 1131-1139 https://doi.org/10.1093/chromsci/bmu175
  13. Jang YA, Lee JT (2018) Anti-wrinkle effect of berberine by inhibition of MMP-2 and MMP-9 activity in fibroblasts. J Appl Biol Chem 61: 9-15 https://doi.org/10.3839/jabc.2018.002
  14. Cha JH, Kim WK, Ha AW, Kim MH, Chang MJ (2017) Antiinflammatory effect of lycopene in SW480 human colorectal cancer cells. Nutr Res Pract 11: 90-96 https://doi.org/10.4162/nrp.2017.11.2.90
  15. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  16. Leal NRF, Vigliano MV, Pinto FA, de Sousa TV, Velozo LSM, Sabino KCC, Justo MDG, Coelho MGP (2018) Anti-inflammatory effect of diterpenes-enriched fractions from Pterodon polygalaeflorus through inhibition of macrophage migration and cytokine production. J Pharm Pharmacol 70: 808-820 https://doi.org/10.1111/jphp.12889
  17. Voller A, Bartlett A, Bidwell DE (1978) Enzyme immunoassays with special reference to ELISA techniques. J Clin Pathol 31: 507-520 https://doi.org/10.1136/jcp.31.6.507
  18. Lee JW, Kang YJ, Choi HK, Yoon YG (2018) Fractionated Coptis chinensis extract and its bioactive component suppress Propionibacterium acnes-stimulated inflammation in human keratinocytes. J Microbiol Biotechnol, doi:10.4014/jmb.1712.12051
  19. Tsai HH, Lee WR, Wang PH, Cheng KT, Chen YC, Shen SC (2013) Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent $NF-{\kappa}B$ and AP-1 activation in macrophages. J Dermatol Sci 69: 122-131 https://doi.org/10.1016/j.jdermsci.2012.10.009
  20. Sharma JN, Al-Omran A, Parvathy SS (2007) Role of nitric oxide in inflammatory diseases. Inflammopharmacol 15: 252-259 https://doi.org/10.1007/s10787-007-0013-x
  21. Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L (2005) Distinct strains of Propionibacterium acnes induce selective human ${\beta}$-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol 124: 931-938 https://doi.org/10.1111/j.0022-202X.2005.23705.x
  22. Qin M, Pirouz A, Kim MH, Krutzik SR, Garban HJ, Kim J (2014) Propionibacterium acnes induces IL-$1{\beta}$ secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol 134: 381-388 https://doi.org/10.1038/jid.2013.309
  23. Lee WR, Kim KH, An HJ, Kim JY, Han SM, Lee KG, Park KK (2014) Protective effect of melittin against inflammation and apoptosis on Propionibacterium acnes-induced human THP-1 monocytic cell. Eur J Pharmacol 740: 218-226 https://doi.org/10.1016/j.ejphar.2014.06.058
  24. Oeckinghaus A, Ghosh S (2009) The $NF-{\kappa}B$ family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1: a000034
  25. Bonizzi G, Karin M (2004) The two $NF-{\kappa}B$ activation pathways and their role in innate and adaptive immunity. Trend Immunol 25: 280-288 https://doi.org/10.1016/j.it.2004.03.008