20.500.12556/DKUM-84054 Vpliv izražanja mmd na odzivnost monocitov in makrofagov na adalimumab in vitro magistrsko delo The effect of mmd expression on the responsiveness of the monocytes and macrophages to adalimumab in vitro Parodontoza je pogosta vnetna bolezen, ki lahko vpliva na slabšo odzivanje bolnikov s sistemskimi boleznimi, kot je revmatoidni artritis, na biološko zdravilo adalimumab. Ugotovljeno je bilo, da stopnja revmatoidnega artritisa korelira z ravnijo izražanja MMD gena v makrofagih izoliranih iz sinovialne tekočine vnetih sklepov. Poleg tega stopnja izražanja MMD vpliva na klinični odziv bolnikov s kronično vnetno črevesno boleznijo na adalimumab. V magistrskem delu smo se odločili preveriti, kako se monociti in iz njih in vitro diferencirani makrofagi bolnikov s parodontozo odzivajo na biološko zdravilo adalimumab ter kakšno vlogo ima pri tem ekspresija MMD. Pri monocitih in iz njih diferenciranih makrofagih smo simulirali vnetje z dodatkom LPS in zdravljenje vnetja s komercialnim biološkim zdravilom adalimumab, ter preverili izražanje vnetnih genov IL1B, IL6 in TNFα. Adalimumab je učinkovito zavrl izražanje genov IL1B in IL6, ki v signalni kaskadi ležita nižje od TNFα, čeprav v primeru IL6 samo za monocite. Na izražanje TNFα dodatek adalimumaba ni imel vpliva. V magistrskem delu nismo dokazali vpliva MMD na učinkovitost adalimumaba pri zaviranju TNFα. Vendar zaradi teh ugotovitev ne moremo ovreči njegove potencialne vloge pri vplivu na učinkovitost adalimumaba, saj je potrebno izvesti še veliko raziskav s spremenjenimi eksperimentalnimi pogoji in tako potrditi ali ovreči vlogo MMD pri neučinkovitosti adalimumaba in s tem pripomoči k izboljšanju zdravljenja vnetnih bolezni. Periodontitis is a common inflammatory disease that may affect the response of patients with systemic diseases such as rheumatoid arthritis to the biologic drug adalimumab. The stage of rheumatoid arthritis was found to correlate with the level of MMD gene expression in macrophages isolated from the synovial fluid of inflamed joints. In addition, the level of MMD expression influences the clinical response of patients with chronic inflammatory bowel disease to adalimumab. In our master's thesis, we decided to check how monocytes and macrophages differentiated from them in vitro from patients with periodontitis respond to the biological drug adalimumab and what role MMD expression plays in this. In monocytes and macrophages differentiated from them, we simulated inflammation with the addition of LPS and the treatment of inflammation with the commercial biological drug adalimumab, and checked the expression of the inflammatory genes IL1B, IL6 and TNFα. Adalimumab effectively inhibited the expression of IL1B and IL6 genes, which lie downstream of TNFα in the signalling cascade, although in the case of IL6 only for monocytes. The expression of TNFα was not affected by adalimumab. In the master's thesis, we did not prove the effect of MMD expression on the effectiveness of adalimumab in inhibiting TNFα. However, due to these findings, we cannot evaluate its potential role in affecting the efficacy of adalimumab, as many more studies with modified experimental conditions are needed to confirm or assess the role of MMD in the ineffectiveness of adalimumab and thus help improve the treatment of inflammatory diseases. MMD parodontoza vnetni citokini adalimumab monociti makrofagi in vitro diferenciacija in vitro vnetje TNFα MMD periodontitis inflammatory cytokines adalimumab monocytes macrophages in vitro differentiation in vitro inflammation TNFα true true false [A. Kralj] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2023-04-03 17:49:15 2023-04-20 07:32:51 2023-05-16 03:08:28 0000-00-00 00:00:00 2023 0 Maribor 0 Maribor 1 spletni vir (1 datoteka PDF (XI, 46 f.)) 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 [577:576.3]+615.281.9.015(043.2) 152123651 MAG_Kralj_Adriana_2023.pdf MAG_Kralj_Adriana_2023.pdf 1 B07290085D714D610B291AF9F89234E7 00a8ce3ae549827f9ba28836d2f115c8a7ecf13b4021ae2dad06340f06324961 6cc05055-deb3-11ed-b3cb-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=166882 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0