Ugotavljanje vpliva polimorfizma posameznega nukleotida (rs4129009) v TLR10 na imunski odziv pljučnih epitelnih celic A549

Rus, Metka (author), Ogorevc, Jernej (mentor)

Tollu podoben receptor 10 (TLR10) je receptor prirojenega imunskega odziva, ki je po svoji funkciji edinstven med receptorji TLR, saj naj bi imel možnost imunomodulatornega delovanja. Med Tollu podobnimi receptorji je bil odkrit zadnji in še vedno spada med tako imenovane receptorje sirote, saj njegovi ligandi in mehanizmi delovanja še niso povsem znani. Pretekle raziskave kažejo, da deluje vnetno, v zadnjem času pa se pojavlja vse več študij, ki poročajo o njegovem protivnetnem delovanju. V raziskavi smo preučevali vpliv polimorfizma rs4129009 in izbitja TLR10 na izražanje genov za vnetne citokine (CXCL10, IL-1β, IL-8 in TNF-α) v pljučnih epitelnih celicah A549 po imunostimulaciji z ligandom Pam3-Cys. Rezultati potrjujejo imunomodulatorno vlogo TLR10, saj pokažejo, da se vnetni citokini v celicah z izbitim TLR10 bolj izražajo kot v celicah s funkcionalnim TLR10. Polimorfizem rs4129009 je oslabil protivnetno delovanje TLR10, saj je statistično značilno zmanjšal inhibicijo izražanja vnetnega CXCL10, zaznali pa smo tudi zmanjšanje izražanja drugih citokinov, vendar spremembe niso bile statistično značilne.

• Language: Slovenian
• Keywords: TLR10, SNP rs4129009, celična linija A549, qPCR
• Work type: Bachelor thesis/paper
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2024
• PID: 20.500.12556/RUL-160976
• Publication date in RUL: 06.09.2024

Secondary language

• Language: English
• Title: Effect of single nucleotide polymorphism (rs4129009) in TLR10 on immune response in A549 cells

Abstract

Toll-like receptor 10 (TLR10) is a receptor of the innate immune system that is unique among TLRs in that it is thought to have immunomodulatory potential. It was the last of the Toll-like receptors to be discovered and is still considered an orphan receptor, as its ligands and mechanisms of action are not yet fully understood. Previous research suggests that its mode of action is pro-inflammatory, but more recent studies report its anti-inflammatory effects. In this study, we investigated the effects of rs4129009 polymorphism and TLR10 knockout on the expression of inflammatory cytokines (CXCL10, IL-1β, IL-8 and TNF-α) in A549 lung epithelial cells immunostimulated with Pam3-Cys. The results confirm an immunomodulatory role of TLR10, as the expression of inflammatory cytokines was higher in the cells with the knocked out gene, compared to the cells with functional TLR10. The rs4129009 polymorphism attenuated the anti-inflammatory effect of TLR10, as it significantly reduced the inhibition of expression of the inflammatory CXCL10. In addition, a decrease in the expression of the other cytokines was observed, but the changes were not statistically significant.

• Keywords: TLR10, SNP rs4129009, cell line A549, qPCR