Karaciğer Fibrozisinde Sitokinlerin Rolü

Year 2021, Volume: 11 Issue: 1, 111 - 122, 01.04.2021

Merve Anapalı , Eda Balkan

Abstract

Karaciğer fibrozisi, hepatik parankimanın farklı bölgelerinde ekstraselüler matriks (ECM) birikimine neden olan α-smooth muscle actin (α-SMA) proteini gibi bir seri proteinin ekspresyonunu başlatan ve esas olarak kolajen üretimi ile ilişkili olan hepatik stellat hücrelerinin (HSCs) aktivasyonu ile karakterize bir hastalıktır. Tüm dünyada yaygın olarak görülen karaciğer fibrozisi; viral enfeksiyonlar, alkol alımı veya metabolik sendrom sebebiyle steatohepatit, otoimmün hastalıklar ve safra tıkanıklığına bağlı olarak kolestaz da dahil olmak üzere çeşitli kronik karaciğer bozukluklarının bir sonucu olarak ortaya çıkmaktadır. Karaciğer fibrozisi, ciddi morbidite oranı ile sonuçlanan önemli bir sağlık sorunudur. Hastalığın patogenezinde hasarlı bölgeye toplanan inflamatuar hücrelerin ve profibrojenik sitokinlerin salınımı kritik rol oynamaktadır. Karaciğer patogenezinde inflamatuar yanıt 3 yolla oluşmaktadır. IL-1β, IL-6, TNF-α ve IFN-γ üretimi ile karakterize olan tip 1 inflamasyon proinflamatuar ve anti-fibrojenik özellikte olup karaciğer inflamasyonu ile ilişkilidir. IL-4, IL-5, IL-10, IL-13, IL-25 ve IL-33 üretimi ile karakterize olan tip 2 inflamasyon karaciğer progresyonu ile ilişkili olup azalan hepatik inflamasyonla ilişkilidir. Mevcut teori tip 1 ve tip 2 inflamasyon arasındaki dengesizliğin karaciğerdeki fibrozisi tetiklediği yönündedir. Tip 3 inflamasyon ise IL-17A, IL-17F, IL-22 ve IL-26, grup 3 başlatıcı lenfoid hücre (ILC3), T yardımcı hücre 17 (Th17) ve T yardımcı hücre 22 (Th22) ile karakterizedir. Tip 3 sitokinler doku homeostazında patolojik olarak önemli bir role sahiptir. Tip 3 immünitede meydana gelen bozukluk anormal doku tamiri, kronik inflamatuar hastalıklar, bağırsak ve akciğer kanserleri ile ilişkilidir. Bu çalışma ile sitokinlerin karaciğer fibrozisi üzerindeki rolünü derlemeyi amaçladık.

Keywords

T lenfosit, Karaciğer fibrozisi, Sitokinler

Role of Cytokines in Liver Fibrosis

Abstract

Liver fibrosis is a characterized by activation of hepatic stellate cells (HSCs) that mainly associated with collagen production which initiate the expression of a series of proteins such as the α-smooth muscle actin (α-SMA) protein that causes accumulation of extracellular matrix (ECM) in different regions of the hepatic parenchyma. In worldwide, Liver fibrosis occurs as a result of various chronic liver disorders including steatohepatitis due to viral infections, alcohol intake or metabolic syndrome, autoimmune diseases and cholestasis due to biliary obstruction. Liver fibrosis is an important health problem that results in severe morbidity. The release of inflammatory cells and profibrogenic cytokines collected in the damaged area plays a critical role in the pathogenesis of the disease. Inflammatory response occurs in 3 ways in liver pathogenesis. Type 1 inflammation which is characterized by the production of IL-1β, IL-6, TNF-α and IFN-γ is proinflammatory, anti-fibrogenic and associated with liver inflammation. Type 2 inflammation characterized by the production of IL-4, IL-5, IL-10, IL-13, IL-25 and IL-33 is associated with liver progression and associated with reduced hepatic inflammation. The current theory is that the imbalance between type 1 and type 2 inflammation triggers liver fibrosis. Type 3 inflammation is characterized by IL-17A, IL-17F, IL-22 and IL-26, group 3 initiating lymphoid cell (ILC3), T helper cell 17 (Th17) and T helper cell 22 (Th22). Type 3 cytokines have a pathologically important role in tissue homeostasis. The disorder that occurs in type 3 immunity is associated with abnormal tissue repair, chronic inflammatory diseases, bowel and lung cancers. In our study, we aim to review the role of cytokines in liver fibrosis.

Keywords

T lymphocyte, Liver fibrosis, Cytokines

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