İnflamazomların Karaciğer Toksisitesindeki Rolü

Abstract

İnflamazomlar, enfeksiyona neden olan mikroorganizmalara ve konak proteinlerinden oluşan moleküllere karşı inflamasyonun başlatılmasından sorumlu olan multiprotein komplekslerdir. Reseptör, adaptör ve efektör proteinlerin bir araya gelmesi sonucu oluşan inflamazomların pirin içeren NOD benzeri reseptör 1 (NLRP1), NLRP2, NLRP3, NLRP6, NLRP10, NLRP12, NLRC4 ve AIM2 olmak üzere 8 farklı tipi tanımlanmıştır. NLRP3 inflamazomu, neredeyse her türlü tehlike sinyalini tanıma özelliğine sahip olmasıyla öne çıkan ve günümüze kadar en fazla araştırılan inflamazomdur. Patojen ilişkili moleküler kalıplar (pathogen-associated moleculer pattern; PAMP) ve hasarlı veya ölen hücrelerin endojen sinyalleri (damage/danger-associated molecular pattern; DAMP) ile aktive olan NLRP3 inflamazomu kaspaz-1 aktive ederek IL-1β ve IL-18 sitokinlerinin salınmasına yol açmaktadır. Karaciğer ilk geçiş organı olmasından ötürü çeşitli mikrobiyal partiküllerle mücadale halindedir. Bu sırada çok sayıda sitozolik patojen, inflamazomlar tarafından algılanabilir. İnflamazomlar, hepatositler, karaciğer sinüzoidal endotel hücreleri, hepatik stellat hücreleri ve makrofajlarda aktif olarak ifade edilir. Patojenlere ve tehlike sinyallerine karşı karaciğer savunması için esas olan inflamazomların aşırı aktivasyonu ise çeşitli karaciğer hastalıklarının patojenezini artırır. Bu derleme kapsamında inflamazomların yapıları, çeşitleri, aktivasyonları ve karaciğer toksisitesinde ki rolleri incelenmiştir.

Keywords

• inflamazom,hepatotoksisite

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