The effects of quercetin on erythropoietin, hypoxia-inducible factors-1α, 2α, and pyroptosis related genes expression levels in inflammation induced by TNF-α and LPS in HepG2 cells

Mete Ozkurt; Burcu Akıncı; Selda Kabadere Deliorman; Rumeysa Özyurt; Abdullah Karadağ; Nilüfer Erkasap

Makale detayları

The effects of quercetin on erythropoietin, hypoxia-inducible factors-1α, 2α, and pyroptosis related genes expression levels in inflammation induced by TNF-α and LPS in HepG2 cells

Yazarlar:

Mete Ozkurt | Burcu Akıncı | Selda Kabadere Deliorman | Rumeysa Özyurt | Abdullah Karadağ | Nilüfer Erkasap

Yayıncı:

Cukurova University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Cukurova Medical Journal Vol.48 Issue 1, pp.268-277

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001282227

pISSN:

2602-3032

Anahtar kelimeler:

Özet:

 Purpose: TNF-α, which increases in the circulation as a result of systemic inflammation, suppresses the production of the erythropoiesis regulating hormone, erythropoietin EPO and causes inflammation anemia. The anti-inflammatory activity of quercetin has been reported in different studies. However, no study has been found showing the effect of this situation on EPO gene expression. For this purpose, we evaluated the effects of quercetin on inflammation and, more importantly, its effects on EPO, suppressed in the inflammatory environment and Hypoxia-inducible factors HIF, which are stimulators of EPO synthesis. In addition, we aimed to evaluate the effect of quercetin on pyroptosis, which is defined as pro-inflammatory programmed cell death. Materials and Methods: We created inflammation models with TNF-α or LPS using HepG2 cells in vitro. In these inflammation models, we evaluated the effects of quercetin on proinflammatory mediators TNF-α, IL-1α, NF-κB gene expressions, EPO, HIF-1α, HIF-2α gene expressions, as well as pyroptosis-related caspase 1 and IL-18 gene expressions. Results: Quercetin showed inflammatory effects by increasing TNF-α, IL-1α, and NF-κB mRNA levels. Consistent with this inflammatory effect, EPO mRNA expression was suppressed. HIF-1α and HIF-2α mRNA levels were increased. Conclusion: These results suggested that the increase in HIFs could not prevent the suppressive effect of inflammatory cytokines and NF-κB on EPO production. However, it has been observed that it tends to suppress proinflammatory cell death by decreasing caspase 1 and IL-18 mRNA levels. These results show that quercetin may show conflicting effects, and further studies are needed to test its safety.

 Purpose: TNF-α, which increases in the circulation as a result of systemic inflammation, suppresses the production of the erythropoiesis regulating hormone, erythropoietin EPO and causes inflammation anemia. The anti-inflammatory activity of quercetin has been reported in different studies. However, no study has been found showing the effect of this situation on EPO gene expression. For this purpose, we evaluated the effects of quercetin on inflammation and, more importantly, its effects on EPO, suppressed in the inflammatory environment and Hypoxia-inducible factors HIF, which are stimulators of EPO synthesis. In addition, we aimed to evaluate the effect of quercetin on pyroptosis, which is defined as pro-inflammatory programmed cell death. Materials and Methods: We created inflammation models with TNF-α or LPS using HepG2 cells in vitro. In these inflammation models, we evaluated the effects of quercetin on proinflammatory mediators TNF-α, IL-1α, NF-κB gene expressions, EPO, HIF-1α, HIF-2α gene expressions, as well as pyroptosis-related caspase 1 and IL-18 gene expressions. Results: Quercetin showed inflammatory effects by increasing TNF-α, IL-1α, and NF-κB mRNA levels. Consistent with this inflammatory effect, EPO mRNA expression was suppressed. HIF-1α and HIF-2α mRNA levels were increased. Conclusion: These results suggested that the increase in HIFs could not prevent the suppressive effect of inflammatory cytokines and NF-κB on EPO production. However, it has been observed that it tends to suppress proinflammatory cell death by decreasing caspase 1 and IL-18 mRNA levels. These results show that quercetin may show conflicting effects, and further studies are needed to test its safety.

 Purpose: TNF-α, which increases in the circulation as a result of systemic inflammation, suppresses the production of the erythropoiesis regulating hormone, erythropoietin EPO and causes inflammation anemia. The anti-inflammatory activity of quercetin has been reported in different studies. However, no study has been found showing the effect of this situation on EPO gene expression. For this purpose, we evaluated the effects of quercetin on inflammation and, more importantly, its effects on EPO, suppressed in the inflammatory environment and Hypoxia-inducible factors HIF, which are stimulators of EPO synthesis. In addition, we aimed to evaluate the effect of quercetin on pyroptosis, which is defined as pro-inflammatory programmed cell death. Materials and Methods: We created inflammation models with TNF-α or LPS using HepG2 cells in vitro. In these inflammation models, we evaluated the effects of quercetin on proinflammatory mediators TNF-α, IL-1α, NF-κB gene expressions, EPO, HIF-1α, HIF-2α gene expressions, as well as pyroptosis-related caspase 1 and IL-18 gene expressions. Results: Quercetin showed inflammatory effects by increasing TNF-α, IL-1α, and NF-κB mRNA levels. Consistent with this inflammatory effect, EPO mRNA expression was suppressed. HIF-1α and HIF-2α mRNA levels were increased. Conclusion: These results suggested that the increase in HIFs could not prevent the suppressive effect of inflammatory cytokines and NF-κB on EPO production. However, it has been observed that it tends to suppress proinflammatory cell death by decreasing caspase 1 and IL-18 mRNA levels. These results show that quercetin may show conflicting effects, and further studies are needed to test its safety.

 Amaç: Sistemik inflamasyon sonucu dolaşımda artan TNF-α, eritropoezi düzenleyici hormon eritropoietin EPO üretimini baskılayarak inflamasyon anemisine neden olur. Quercetinin antiinflamatuar aktivitesi farklı çalışmalarda rapor edilmiş ancak bu durumun EPO gen ekspresyonu üzerine etkisini gösteren bir çalışmaya rastlanmamıştır. Bu amaçla quercetinin inflamasyon ve daha da önemlisi inflamatuar ortamda baskılanan EPO ve EPO sentezini uyaran Hipoksi ile indüklenebilir faktörler HIF üzerindeki etkilerini değerlendirdik. Ayrıca proinflamatuvar programlı hücre ölümü olarak tanımlanan piroptozis üzerine quercetinin etkisini değerlendirmeyi amaçladık. Gereç ve Yöntem: İn-vitro HepG2 hücrelerini kullanarak TNF-α veya LPS ile inflamasyon modelleri oluşturduk. Bu inflamasyon modellerinde, quercetinin proinflamatuar mediatörler TNF-α, IL-1α, NF-κB gen ekspresyonları, EPO, HIF-1α, HIF-2α gen ekspresyonları ve ayrıca piroptozla ilişkili kaspaz-1 ve IL-18 gen ifadesi üzerindeki etkilerini değerlendirdik.. Bulgular: Quercetin, TNF-α, IL-1α, NF-κB mRNA düzeylerini yükselterek inflamatuar etkiler göstermiştir. Bu enflamatuar etkiyle uyumlu olarak, EPO mRNA ekspresyonu baskılanmıştır. HIF-1α ve HIF-2α mRNA seviyeleri yükselmiştir. Sonuç: HIFlerdeki artışın, inflamatuar sitokinlerin ve NF-κBnin EPO üretimi üzerindeki baskılayıcı etkisini engelleyemediğini düşündürmektedir. Ancak kaspaz-1 ve IL-18 mRNA düzeylerini düşürerek proinflamatuar hücre ölümünü baskılama eğiliminde olduğu gözlemlenmiştir. Bu sonuçlar, quercetinin çelişkili etkiler gösterebileceğini ve güvenliğini test etmek için daha ileri çalışmalara ihtiyaç olduğunu göstermektedir.

Makale detayları

The effects of quercetin on erythropoietin, hypoxia-inducible factors-1α, 2α, and pyroptosis related genes expression levels in inflammation induced by TNF-α and LPS in HepG2 cells

Yazarlar:

Mete Ozkurt | Burcu Akıncı | Selda Kabadere Deliorman | Rumeysa Özyurt | Abdullah Karadağ | Nilüfer Erkasap

Yayıncı:

Cukurova University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Cukurova Medical Journal Vol.48 Issue 1, pp.268-277

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001282227

pISSN:

2602-3032

anemia of inflammation

erythropoietin

HIF

TNF-alpha

quercetin

inflamasyon anemisi

eritropoetin

HİF

TNF-alfa

quercetin

Sayı

Makale detayları

Yazarlar: Mete Ozkurt | Burcu Akıncı | Selda Kabadere Deliorman | Rumeysa Özyurt | Abdullah Karadağ | Nilüfer Erkasap

Yayıncı: Cukurova University

Ana Başlıklar: Klinik Tıp Bilimleri

Dergi: Cukurova Medical Journal Vol.48 Issue 1, pp.268-277

Belge Tipi: Makale

Yayın Tarihi: 3/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001282227

pISSN: 2602-3032

Sayı

Yazarlar:

Mete Ozkurt | Burcu Akıncı | Selda Kabadere Deliorman | Rumeysa Özyurt | Abdullah Karadağ | Nilüfer Erkasap

Yayıncı:

Cukurova University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Cukurova Medical Journal Vol.48 Issue 1, pp.268-277

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001282227

pISSN:

2602-3032