Utjecaj citokina TNF-alfa i IFN-gama na ekspresiju gena REL, CXCL10 i PD-L1 u staničnim linijama Farage i U2940

master's thesis

• Title (english): The effect of cytokines TNF-alpha and IFN-gamma on REL, CXCL10 and PD-L1 gene expression in Farage and U2940 cell lines
• Author: Anja Krstulović
• Mentor: Petra Korać (mentor)
• Mentor: Paula Gršković (komentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-02-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Stanice imunosnog sustava posredstvom specifičnih receptora i signalnih molekula citokina reguliraju i aktiviraju imunosni odgovor. Aktivacijom raznih signalnih putova dolazi do aktivacije i diferencijacije imunosnih stanica u zrele i efektorske oblike. Faktor tumorske nekroze alfa (TNF-α, od engl. tumour necrosis factor) aktivira signalni put NF-κB, regulira ekspresiju posredničkih molekula i imunosnim stanicama omogućuje migraciju. Interferon gama (IFN-γ) aktivira signalni put JAK-STAT, utječe na ekspresiju kemokina i molekula glavnog sustava tkivne podudarnosti (MHC, od engl. major histocompatibility complex) te na aktivaciju imunosnih stanica. Procesi diferencijacije imunosne stanice čine tolerantnijima prema nakupljanju promjena u genomu i nepravilnoj transformaciji, koja može dovesti do nastanka limfoma. Primarni medijastinalni B-stanični limfom (PMBL) spada u skupinu ne-Hodgkinovih limfoma (NHL), a nastaje od B-limfocita smještenih u medijastinumu. U ovom radu istražen je utjecaj citokina TNF-α i IFN-γ na razinu ekspresije gena REL, CXCL10 i PDL1 u modelnim staničnim linijama. Gen REL kodira protein c-Rel, transkripcijski faktor signalnog puta NF-κB. Gen CXCL10 kodira istoimeni kemokin. Gen PDL1 kodira protein koji sudjeluje u mehanizmu koji regulira odgovor T-limfocita. Tretman citokinom IFN-γ povećavao je ekspresiju gena CXCL10 kod obje stanične linije, a ekspresiju gena PDL1 samo kod jedne stanične linije. Tretmani citokinom TNF-α pokazali su mješovite rezultate između staničnih linija za gen CXCL10 te većinom uzrokovali smanjenje ekspresije gena PDL1 i REL. Varijabilnost ekspresije istraživanih gena ukazuje na veliku heterogenost primarnog medijastinalnog limfoma.

Abstract (english)

Immune cells regulate the immune response by interacting with specific receptors expressed on their surface and by secreting cytokines. Tumour necrosis factor alpha (TNF-α) activates the NF-κB signalling pathway, regulates the expression of mediators and enables the migration of immune cells. Interferon-gamma (IFN-γ) activates the JAK-STAT signalling pathway and influences the expression of chemokines and proteins of the major histocompatibility complex (MHC) and the activation of immune cells. The processes that immune cells undergo during their differentiation can contribute to abnormal transformations and the formation of lymphomas. Primary mediastinal large B-cell lymphoma (PMBL), a form of non-Hodgkin's lymphoma (NHL), arises from B-cells located in the mediastinum. The aim of this study was to investigate the effect of cytokines TNF-α and IFN-γ on the expression of REL, CXCL10 and PDL1 genes in PMBL model cell lines. The REL gene encodes the c-REL transcription factor of the NF-κB signalling pathway. The CXCL10 gene codes for a chemokine. The PDL1 gene codes for a protein that plays a decisive role in the regulatory mechanism of the T-cell immune response. IFN-γ caused an increase in CXCL10 gene expression in both cell lines and PDL1 gene expression in one cell line. TNF-α, on the other hand, showed ambiguous results for the CXCL10 gene and predominately caused a decrease in gene expression of PDL1 and REL genes. The variability of the expression of the investigated genes indicates the significant heterogeneity of primary mediastinal lymphoma.

• Keywords: primarni medijastinalni B-stanični limfom; signalni put JAK-STAT; signalni put NF-κB
• Keywords (english): primary mediastinal B-cell lymphoma; JAK-STAT signal pathway; NF-κB signal pathway
• Language: croatian
• URN:NBN: urn:nbn:hr:217:835797
• Study programme: Title: Molecular Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra molekularne biologije (sveučilišni/a magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-02-16
• Created on: 2024-03-08 10:52:09