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Title: The mechanisms involved in intercellular adhesion molecule 1 and hyaluronan synthase 2 induction following monocyte-fibroblast interaction
Author: Chaudhri, Saurabh
ISNI:       0000 0004 5917 7206
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2015
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)