Research Article
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Ferulik asitin lipopolisakkaridaz ile induklenmiş insan lösemi monositik hücrelerinde sitokin salınımına etkisi

Year 2021, Volume: 60 Issue: 1, 39 - 50, 31.03.2021

Şahin Öztürk , Burak Durmaz , Hikmet Memmedov , Latife Merve Oktay , Nur Selvi Günel , Murat Olukman , Eser Y. Sözmen

https://doi.org/10.19161/etd.887360

Abstract

Amaç: Makrofajlar doğal immün cevabı başlatan ve patojenle ilk temasta bulunan hücreler olarak kabul edilmektedir. Hem hücreler arası ilişkiler hem de inflamatuar mediyatörlerin salınımı yoluyla doğal immün ve inflamatuar yanıtta etkin rol oynamaktadırlar. İnsan THP-1 lösemi monositik hücreleri, makrofajların in vitro olarak fonksiyonlarını, mekanizmalarını ve sinyal yollarını araştırmak için en çok kullanılan hücre dizisidir. Lipopolisakkarid (LPS) makrofaj farklılaşmasını başlatmak için yaygın olarak kullanılan uyarıcılar arasında yer almaktadır. Ferulik asid (FA)'in, indüklenebilir nitrik oksit sentaz, kaspazlar ve siklooksijenaz (COX)-2 dahil olmak üzere proinflamatuar sitokinlerin ekspresyonunu ve/veya aktivitesini inhibe ettiği bilinmektedir. Bu çalışmada, LPS ile indüklenen THP-1 monosit hücrelerinde Ferulik asidin sitokin (COX-1, IL-lα, IL-1β, TNF-α, IL-6, IL-10, NF-kβ ve IFN-y) düzeyleri üzerindeki etkisini araştırmayı amaçladık.
Gereç ve Yöntem: TNF alfa seviyeleri farklı konsantrasyonlarda ve zamanlarda LPS eklenerek ölçüldü ve en uygun konsantrasyon ve süre belirlendi. COX-1, IL-lα, IL-lβ, TNF-α, IL-6, IL-10, NF-kβ ve IFN-y'nin sitokin miktarları, inkübasyon sürelerinin sonunda toplanan süpernatanlarda ELISA ile ölçüldü.
Bulgular: Ferulik asidin, NF-kβ inhibisyonu ile LPS ile indüklenen THP-1 hücrelerinde artan TNF-α, IL-lα ve IL-lβ ekspresyonunu inhibe ettiğini bulduk.
Sonuç: Ferulik asidin LPS ile indüklenen THP-1 hücrelerinde sitokin salınımı üzerindeki etkisinin gösterilmesi, aşırı inflamatuar yanıtın tedavisinde ve oto-immün hastalıklara karşı korunmada etkili olabileceğini düşündürdü

Keywords

THP-1 hücreleri sitokin lipopolisakkarit makrofaj hücreleri

Supporting Institution

EGE ÜNİVERSİTESİ BAP ( Bilimsel Araştırma Projesi)

Thanks

Bu çalışma EGE ÜNİVERSİTESİ BAP ( Bilimsel Araştırma Projesi) tarafından desteklenmiştir, bu projedeki destekleri için teşekkür ederiz (Proje 16-TIP-049). Yazarlar, teknik yardımlarından dolayı Ege Üniversitesi Çocuk Hastanesi Metabolizma Laboratuvarı'na çok teşekkür ederiz.

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  • Szulc-Kielbik, I., Kielbik, M., & Klink, M. (2017). Ferulic acid but not alpha-lipoic acid effectively protects THP-1-derived macrophages from oxidant and pro-inflammatory response to LPS. Immunopharmacology and Immunotoxicology, 39 (6), 330-337.
  • Zhang, S., Wang, P., Zhao, P., Wang, D., Zhang, Y., Wang, J., et al. (2018). Pretreatment of ferulic acid attenuates inflammation and oxidative stress in a rat model of lipopolysaccharide-induced acute respiratory distress syndrome. International journal of immunopathology and pharmacology, 31, 0394632017750518.
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Effect of ferulic acid on cytokine release in human leukemia monocytic cells induced with lipopolysaccharides

Year 2021, Volume: 60 Issue: 1, 39 - 50, 31.03.2021

Şahin Öztürk , Burak Durmaz , Hikmet Memmedov , Latife Merve Oktay , Nur Selvi Günel , Murat Olukman , Eser Y. Sözmen

https://doi.org/10.19161/etd.887360

Abstract

Aim: Macrophages are accepted as cells that initially contact with the pathogens and initiate the innate immune response. They play effective roles in innate immune and inflammatory responses by intercellular relations and inflammatory mediator secretion. Human THP-1 leukemia monocytic cells are frequently used for the in vitro determination of the signal pathways, and the functions of macrophages. Lipopolysaccharide is commonly used to induce macrophage differentiation of monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear.
Ferulic acid (FA) is known to inhibit the expression and / or activity of proinflammatory cytokines, including inducible nitric oxide synthase, caspases, and cyclooxygenase (COX)-2. In this study, we aimed to investigate the effect of Ferulic acid on cytokine (COX-1, IL-1α, IL-1β, TNF-α, IL-6, IL-10, NF-kβ and IFN-γ) levels in lipopolysaccharide induced THP-1 monocyte cells.
Materials and Methods: TNF alpha levels were measured by performing applications at different concentrations and times, and the most appropriate concentration and duration were determined. Cytokine levels of COX-1, IL-1α, IL-1β, TNF-α, IL-6, IL-10, NF-kβ and IFN-γ were measured by ELISA in supernatants collected at the end of incubation times from wells.
Results: We have found that ferulic acid inhibits the expression of TNF-α, IL-1α and IL-1β in LPS-induced macrophages by inhibition of NF-kB.
Conclusion: It has been found that the effect of ferulic acid on cytokine release in LPS-induced THP-1 cells may be effective in the treatment of excessive inflammatory response and protection against auto-immune diseases.

Keywords

THP-1 Cells cytokine LPS macrophage cell

References

  • D'Archivio, M., Filesi, C., Di Benedetto, R., Gargiulo, R., Giovannini, C. and Masella, R. (2007). Polyphenols, dietary sources and bioavailability. Annali dell'Istituto Superiore di Sanita, 43 (4), 348–361.
  • Rondini L., Peyrat-Maillard M.-N., Marsset-Baglieri A., and Berset C., (2002). Sulfated ferulic acid is the main in vivo metabolite found after short-term ingestion of free ferulic acid in rats. Journal of Agricultural and Food Chemistry, 50 (10), 3037–3041.
  • Mancuso, C., & Santangelo, R. (2014). Ferulic acid: pharmacological and toxicological aspects. Food and Chemical Toxicology, 65, 185-195.
  • Kundu, J. K., & Surh, Y. J. (2008). Inflammation: gearing the journey to cancer. Mutation Research/Reviews in Mutation Research, 659 (1-2), 15-30.
  • Larsen, G. L., & Henson, P. M. (1983). Mediators of inflammation. Annual review of immunology, 1 (1), 335-359.
  • Erwig, L. P., & Rees, A. J. (1999). Macrophage activation and programming and its role for macrophage function in glomerular inflammation. Kidney and Blood Pressure Research, 22 (1-2), 21-25.
  • Lawrence, T., Willoughby, D. A., & Gilroy, D. W. (2002). Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nature Reviews Immunology, 2 (10), 787-795.
  • Kobayashi, S. D., Voyich, J. M. Burlak, C., & DeLeo, F. R. (2005). Neutrophils in the innate immune response. Archıvum Immunologıae Et Therapıae Experımentalıs-Englısh Edıtıon, 53 (6), 505.
  • Italiani, P., & Boraschi, D. (2014). From monocytes to M1/M2 macrophages: phenotypical vs. functional differentiation. Frontiers in immunology, 5, 514.
  • Wang, J. Q., Jeelall, Y. S., Ferguson, L. L., & Horikawa, K. (2014). Toll-like receptors and cancer: MYD88 mutation and inflammation. Frontiers in immunology, 5, 367.
  • Lu, Y. C., Yeh, W. C., & Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine, 42 (2), 145-151.
  • Boshtam M., Asgary S., Kouhpayeh, S., Shariati, L., & Khanahmad, H. (2017). Aptamers against pro-and anti-inflammatory cytokines: a review. Inflammation, 40 (1), 340-349.
  • González R., Ballester I., López-Posadas, R., Suárez, M. D., Zarzuelo, A., Martinez-Augustin, O.et al. (2011). Effects of flavonoids and other polyphenols on inflammation. Critical reviews in food science and nutrition, 51 (4), 331-362.
  • Comalada, M., Ballester, I., Bailon, E., Sierra, S., Xaus, J., Gálvez, J. et al. (2006). Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure–activity relationship. Biochemical pharmacology, 72 (8), 1010-1021.
  • Blonska, M., Czuba, Z. P., & Krol, W. (2003). Effect of Flavone Derivatives on Interleukin‐1β (IL‐1β) mRNA Expression and IL‐1β Protein Synthesis in Stimulated RAW 264.7 Macrophages. Scandinavian Journal of Immunology, 57 (2), 162-166.
  • Sharma, V., Mishra, M., Ghosh, S., Tewari, R., Basu, A., Seth, P.,et al. (2007). Modulation of interleukin-1β mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain research bulletin, 73 (1-3), 55-63.
  • Min, Y. D., Choi, C. H., Bark, H., Son, H. Y., Park, H. H., Lee, S., et al. (2007). Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-κB and p38 MAPK in HMC-1 human mast cell line. Inflammation Research, 56 (5), 210-215.
  • Lyu, S. Y., & Park, W. B. (2005). Production of cytokine and NO by RAW 264.7 macrophages and PBMC in vitro incubation with flavonoids. Archives of pharmacal research, 28 (5), 573.
  • Drummond, E. M., Harbourne, N., Marete, E., Martyn, D., Jacquier, J. C., O'Riordan, D.,et al. (2013). Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark. Phytotherapy Research, 27 (4), 588-594.
  • Schindler, R., Mancilla, J., Endres, S., Ghorbani, R., Clark, S. C., & Dinarello, C. A. (1990). Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood, 75, 40-47
  • Essafi-Benkhadir, K., Refai, A., Riahi, I., Fattouch, S., Karoui, H., & Essafi, M. (2012). Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-κB, p38MAPK and Akt inhibition. Biochemical and Biophysical Research Communications, 418 (1), 180-185.
  • Okamoto, I., Iwaki, K., Koya-Miyata, S., Tanimoto, T., Kohno, K., Ikeda, M., & Kurimoto, M. (2002). The flavonoid Kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+ T cell engraftment. Clinical immunology, 103 (2), 132-144.
  • Yahfoufi, N., Alsadi, N., Jambi, M., & Matar, C. (2018). The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10 (11), 1618.
  • Beeson, P. B. (1948). Temperature-elevating effect of a substance obtained from polymorphonuclear leucocytes. The Journal of clinical investigation, 27 (4), 524
  • Gery, I., Gershon, R. K., & Waksman, B. H. (1972). Potentiation of the T-lymphocyte response to mitogens: I. The responding cell. The Journal of experimental medicine, 136 (1), 128-142.
  • Baskaran, N., Manoharan, S., Balakrishnan, S., & Pugalendhi, P. (2010). Chemopreventive potential of ferulic acid in 7, 12-dimethylbenz [a] anthracene-induced mammary carcinogenesis in Sprague–Dawley rats. European journal of pharmacology, 637 (1-3), 22-29.
  • Murakami, A., Nakamura, Y., Koshimizu, K., Takahashi, D., Matsumoto, K., Hagihara, K., et al.(2002). FA15, a hydrophobic derivative of ferulic acid, suppresses inflammatory responses and skin tumor promotion: comparison with ferulic acid. Cancer Letters, 180 (2), 121-129.
  • Graf, E. (1992). Antioxidant potential of ferulic acid. Free radical biology and medicine, 13 (4), 435-448.
  • Wang, B., & Trayhurn, P. (2006). Acute and prolonged effects of TNF-α on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture. Pflügers Archiv, 452 (4), 418-427.
  • Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996). IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α-and obesity-induced insulin resistance. Science, 271 (5249), 665-670.
  • Gerin, F., Erman, H., Erboga, M., Sener, U., Yilmaz, A., Seyhan, H., et al. (2016). The effects of ferulic acid against oxidative stress and inflammation in formaldehyde-induced hepatotoxicity. Inflammation, 39(4), 1377-1386.
  • Szulc-Kielbik, I., Kielbik, M., & Klink, M. (2017). Ferulic acid but not alpha-lipoic acid effectively protects THP-1-derived macrophages from oxidant and pro-inflammatory response to LPS. Immunopharmacology and Immunotoxicology, 39 (6), 330-337.
  • Zhang, S., Wang, P., Zhao, P., Wang, D., Zhang, Y., Wang, J., et al. (2018). Pretreatment of ferulic acid attenuates inflammation and oxidative stress in a rat model of lipopolysaccharide-induced acute respiratory distress syndrome. International journal of immunopathology and pharmacology, 31, 0394632017750518.
  • Mosley, B., Urdal, D. L., Prickett, K. S., Larsen, A., Cosman, D., Conlon, P. J., et al. (1987). The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. Journal of biological chemistry, 262 (7), 2941-2944.
  • Kim, B., Lee, Y., Kim, E., Kwak, A., Ryoo, S., Bae, S., et al. (2013). The interleukin-1α precursor is biologically active and is likely a key alarmin in the IL-1 family of cytokines. Frontiers in immunology, 4, 391.
  • Beer, H. D., Contassot, E., & French, L. E. (2014). The inflammasomes in autoinflammatory diseases with skin involvement. Journal of Investigative Dermatology, 134 (7), 1805-1810.
  • Gerondakis, S., Grumont, R., Gugasyan, R., Wong, L., Isomura, I., Ho, W., et al. (2006). Unravelling the complexities of the NF-κ B signalling pathway using mouse knockout and transgenic models. Oncogene, 25(51), 6781-6799.
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There are 56 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Articles
Authors

Şahin Öztürk 0000-0002-5793-4993

Burak Durmaz 0000-0002-5285-3641

Hikmet Memmedov 0000-0002-8012-0445

Latife Merve Oktay 0000-0002-7110-3379

Nur Selvi Günel 0000-0003-0612-2263

Murat Olukman 0000-0002-9868-4716

Eser Y. Sözmen 0000-0002-6383-6724

Publication Date March 31, 2021
Submission Date October 20, 2020
Published in Issue Year 2021Volume: 60 Issue: 1

Cite

Vancouver Öztürk Ş, Durmaz B, Memmedov H, Oktay LM, Selvi Günel N, Olukman M, Y. Sözmen E. Ferulik asitin lipopolisakkaridaz ile induklenmiş insan lösemi monositik hücrelerinde sitokin salınımına etkisi. EJM. 2021;60(1):39-50.
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