The Role Of Stromal Cell Derived Interleukin-10 In Hepatic Stellate Cell And Macrophage Interactions In Liver Fibrosis
BSc (Intercalated) Dissertation, University of Southampton · 1998 · doi:10.5281/zenodo.17358078 · doi:10.17613/hbkf5-gfz21
Plain-language summary
This is Dr Marathe's undergraduate intercalated degree research project — the foundational work behind the 1998 Hepatology paper listed on this site. Using rat and mouse liver stellate cells cultured in the lab, the project characterised in detail exactly when and how much IL-10 these cells produce as they activate, and showed that this IL-10 measurably suppresses inflammatory signalling (TNF-α production) in macrophages — an effect that could be reversed by neutralising the IL-10.
Why this matters
This thesis contains the original experimental groundwork later condensed into the peer-reviewed Hepatology paper. It is now permanently archived and independently citable via Zenodo, giving the underlying data and methodology a stable, citable home distinct from the shorter journal version.
Published abstract
Hepatic fibrosis is the common end-point of a diverse range of chronic parenchymal liver injury, and is a major world-wide medical problem, presently with no specific medical treatment. The central process in liver fibrosis is the phenotypic transformation (activation) of the hepatic stellate cell (HSC) from a quiescent vitamin A storing phenotype to a myofibroblastic phenotype. HSC activation occurs as a result of interactions between HSC and resident hepatic macrophages (Kupffer cells). This project confirmed and quantitatively characterised expression of IL-10 protein during HSC activation in vitro, compared basal versus induced production of IL-10 in HSC, and examined the effects of HSC-derived IL-10 on macrophage function. IL-10 was detected in unstimulated rat HSC conditioned medium at 180-1300pg/ml during days 0-14 post-isolation, followed by a reduction thereafter, associated with increased lysate IL-10. A reduction in TNF-α production by LPS-stimulated macrophages was observed on pre-exposure to live HSC and HSC-conditioned medium, an effect reduced by neutralising anti-IL-10 antibody. Rat and murine HSC express IL-10 protein during activation on plastic, and HSC can down-regulate macrophage activity via IL-10, an axis potentially important for future therapeutic strategies.
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Keywords
interleukin-10 hepatic stellate cells Kupffer cells liver fibrosis thesis
Cite this thesis
Marathe M. The Role Of Stromal Cell Derived Interleukin-10 In Hepatic Stellate Cell And Macrophage Interactions In Liver Fibrosis [dissertation]. BSc (Intercalated) Dissertation, University of Southampton; 1998. doi:10.5281/zenodo.17358078Copied!