Şahin ÖZTÜRK, Burak DURMAZ, Hikmet MEMMEDOV, Latife Merve OKTAY, Selvi Nur GÜNEL, Murat OLUKMAN, Eser YILDIRIM SÖZEN

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

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. Lipopolisakkarit makrofaj farklılaşmasını başlatmak için yaygın olarak kullanılan uyarıcılar arasında yer almaktadır. Ferulik asidin, indüklenebilir nitrik oksit sentaz, kaspazlar ve siklooksijenaz (COX)-2 dahil olmak üzere proinflamatuar sitokinlerin ekspresyonunu ve/veya aktivitesini inhibe ettiği bilinmektedir. Bu çalışmada, lipopolisakkarit 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 lipopolisakkarit 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

Effect of ferulic acid on cytokine release in human leukemia monocytic cells induced with lipopolysaccharides

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.

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