Use this URL to cite or link to this record in EThOS:
Title: Studies on cytokines in liver pathophysiology
Author: Simpson, Kenneth J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Aims of the thesis: To study the mechanisms of chemokine production that may occur during hepatic disease, the role of chemokines in hepatic injury and repair following paracetamol poisoning and hepatic expression of chemokines in patients with liver disease. In addition, the roles of tumour necrosis factor alpha (TNF) and stem cell factor (SCF) were also studied following paracetamol poisoning. Results: Both CXC and CC chemokines were produced during monocyte adhesion with human hepatoma cell lines. IL-8 production was dependent on proinflammatory cytokine production. In contrast, CC chemokine production appeared to be dependent on free radical activation of NF-κB. Direct TNF stimulated IL-8 production was mediated by TNF RI receptors via a protein kinase C pathway and was inhibited by dexamethasone. Both CXC and CC chemokines were detectable in human liver biopsies in patients with hepatitis C, hepatic allograft rejection and alcoholic hepatitis. Hepatic CXC and CC chemokines were also induced following paracetamol poisoning, inhibition of MIP2 and MIP1 alpha increased 3 day mortality and augmenting MIP2 expression was associated with accelerated hepatic regeneration. Hepatic TNF expression was not induced following paracetamol poisoning and inhibiting TNF was not associated with protection from hepatic injury. SCF was present within the liver at high concentration and located in both hepatocytes and bile ducts. Paracetamol poisoning was associated with reduced hepatic SCF concentrations and inhibiting SCF was associated with delayed hepatic regeneration. Conclusions: Both adhesion mediated and direct proinflammatory cytokine stimulation induce hepatic chemokine production. Chemokines are expressed in liver tissue from patients with hepatitis and therefore may be implicated in the pathogenesis of hepatic inflammation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available