NF-κB Regulates MCP-1 and Eotaxin Expression in TNF-α and IL-1β Stimulated Human Gingival Fibroblasts
Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
The transcription factor nuclear factor κB (NF-κB) is a family of proteins, which regulates several cellular processes. Deficiencies in the function of NF-κB have been shown to play a crucial role in inflammatory response and -diseases. Periodontitis is a disease where gum-inflammation causes destruction of tooth supporting tissues and jeopardizes tooth retention in the jaws. Cytokines and chemokines are shown to play a decisive role in the pathogenesis of periodontitis. The aim of this study was to investigate the intracellular signaling pathways of NF-κB in primary human gingival fibroblasts stimulated with pro-inflammatory cytokines, and to explore the possible role of NF-κB in chemokine expression of these cells.
Gingival fibroblasts isolated from periodontally healthy individuals were cultured in vitro and incubated with or without the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) or interleukin 1β (IL-1β). Quantitative PCR (qPCR) analyses showed thatTNF-α and IL-1β caused an increased mRNA expression of theNF-κB p50. Moreover, a time-dependent decrease of theNF-κB inhibitory proteinIκB-α was shown by western blot.TNF-α and IL-1β caused a time-dependent increased mRNA expression of the chemokines eotaxin and monocyte chemotactic protein-1 (MCP-1), and addition of pharmacological inhibitors of NF-κB, BMS-345541 or Celastrol, reduced the eotaxin and MCP-1 expression by 40% and 50-70% respectively. These results point toward that activation of the NF-κB signaling pathway is critical for increased expression of eotaxin and MCP-1 in human gingival fibroblasts exposed to the pro-inflammatory cytokines TNF-α and IL-1β.
Place, publisher, year, edition, pages
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-113658OAI: oai:DiVA.org:umu-113658DiVA: diva2:886924