An influx of leucocytes, particularly macrophages, into the glomerulus and cortical interstitium, is characteristic of most forms of progressive renal disease. Previous work in our lab has demonstrated that leucocyte adherence to primary cultures of human renal fibroblasts stimulated ICAM-1 induction (1). Induction was initiated as a result of the ICAM-1/ β2 integrin interaction, and was mimicked by crosslinking ICAM-1 with specific antibodies. The aim of my research was to examine the effect of leucocyte/fibroblasts interaction on ICAM-1 and HAS2 expression, and to investigate the mechanisms involved. I have shown induction of HAS 2 mRNA, the principal synthase involved in generation of the extracellular matrix polysaccharide hyaluronan (HA), in parallel with ICAM-1 in the fibroblasts. There were both cell-contact and soluble factor-mediated components to this activation. In addition there was an exponential rise in this induction when monocytes were activated. This was mediated by ICAM-1 on the fibroblast surface. Two major pro-inflammatory cytokines, TNFα and IL 1β, were shown to be potential soluble factor involved. In conclusion, I was able to show two possible mechanisms through which mononuclear cells activate fibroblasts and induce ICAM 1 and HAS 2, thus perpetuating an inflammatory reaction. The first was through interaction with ICAM-1 on the fibroblast surface the second was through the release of pro-inflammatory cytokines.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:683653 |
| Date | January 2015 |
| Creators | Chaudhri, Saurabh |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/89040/ |
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