Roelofs, AnkeAljumah, Eman Jumah2024-12-182024https://hdl.handle.net/20.500.14154/74316Giant cell arteritis (GCA) is a chronic autoimmune vasculitis primarily affecting large and medium arteries in individuals over 50 years of age. This study investigated the pro-inflammatory roles of interleukin-6 (IL-6) and interleukin-12 (IL-12) in human aortic adventitial fibroblasts (HAoAF) within the context of GCA, with a focus on their influence on gene expression (quantitative polymerase chain reaction) and cell viability (alamarBlue™). The study findings suggested that IL-6 plays a significant role in enhancing chemokine production and promoting matrix remodeling in HAoAF cells, potentially driving the inflammatory processes and tissue remodeling that are characteristic of GCA. In contrast, IL-12 exhibited a more nuanced, possibly suppressive, effect on certain inflammatory genes, suggesting that its involvement in GCA may be more complex, possibly by modulation of fibroblast responses rather than directly fuelling inflammation. This study enhances our understanding of the role of vascular fibroblasts in GCA and underscores the potential use of IL-6 and IL-12 as therapeutic targets in managing chronic inflammation associated with GCA.Giant cell arteritis (GCA) is a chronic autoimmune vasculitis primarily affecting large and medium arteries in individuals over 50 years of age. This study investigated the pro-inflammatory roles of interleukin-6 (IL-6) and interleukin-12 (IL-12) in human aortic adventitial fibroblasts (HAoAF) within the context of GCA, with a focus on their influence on gene expression (quantitative polymerase chain reaction) and cell viability (alamarBlue™). The study findings suggested that IL-6 plays a significant role in enhancing chemokine production and promoting matrix remodeling in HAoAF cells, potentially driving the inflammatory processes and tissue remodeling that are characteristic of GCA. In contrast, IL-12 exhibited a more nuanced, possibly suppressive, effect on certain inflammatory genes, suggesting that its involvement in GCA may be more complex, possibly by modulation of fibroblast responses rather than directly fuelling inflammation. This study enhances our understanding of the role of vascular fibroblasts in GCA and underscores the potential use of IL-6 and IL-12 as therapeutic targets in managing chronic inflammation associated with GCA.33en(AlamarBlue) AlamarBlue Assay. (CCL2) C-C Motif Chemokine Ligand 2. (CSF1) Colony Stimulating Factor 1 (also known as Macrophage Colony-Stimulating FactorM-CSF). (CXCL10) C-X-C Motif Chemokine Ligand 10. (DMEMGibcoThermo Fisher Scientific) Dulbecco's Modified Eagle Medium (GCA) Giant cell arteritis. GM-CSF: Granulocyte-Macrophage Colony-Stimulating Factor. (The housekeeping gene GAPDH) Glyceraldehyde-3-Phosphate Dehydrogenase. (HAoAF) Human Aortic Adventitial Fibroblasts. (HSF) Human Synovial Fibroblasts. IFN-γ: Interferon gamma. (IL6) Interleukin 6. (IL12) Interleukin 12 Interleukin 12 Subunit Alpha. IL-23: Interleukin 23. (IL18) Interleukin 18. (MMP2) Matrix Metallopeptidase 2. (MMP14) Matrix Metallopeptidase 14. (qPCR) Real-time quantitative RT-PCR. Th0: Naive T helper cells. Th1: T helper type 1 cells. Th17: T helper type 17 cells.Thesis