Author: Mithil Chokshi

Publisher:

Published: 2010

Total Pages:

ISBN-13:

The purpose of this research project is to study the signaling pathways of the inflammatory cytokines - Interleukin-1 (IL-1) and Interleukin-6 (IL-6) - and investigate any "cross-talk" between the two. IL-6 plays a central role in the Non-Alcoholic Fatty Liver Disease (NAFLD) and we hypothesize that the progression of NAFLD is caused by the imbalance in downstream transcription factor activity of IL-1 and IL-6. Thus, investigating the possible cross-talk would be beneficial in assessing this imbalance. According to the previous work done by the research group, green fluorescent protein (GFP) reporter plasmids with STAT3 and C/EBP[beta] transcription factor binding sequences were transfected into human hepatocarcinoma (HepG2) cells. Once they were stimulated with cytokines IL-6 or IL-10, they were analyzed with fluorescence microscopy which showed that the transcription factors STAT3 and C/EBP[beta] were activated leading to a corresponding expression of GFP. This research project will be focused on the dynamics of IL-6 and the effects of IL-1 (instead of IL-10) on it. IL-1 and IL-6 are both involved in many inflammatory responses of the body and by having a deeper understanding about their pathways to initiation of the inflammatory responses and any interconnections will help us model a feedback system to control the response. The findings will assist in finding a therapeutic approach to mitigate various inflammatory diseases where IL-1 and IL-6 play a major role in (e.g. NAFLD). In addition, these results will also be useful in bioengineering. Inflammatory response of the body towards any bioengineered implants mediated by these cytokines could be controlled on a molecular level. Thus, instead of wasting thousands of dollars on coming up with a new design, bioengineers can manipulate the body's response and use the device that was formerly rejected by the body. Research will be conducted to 1) quantify the transcription factor activity, 2) study the dynamics of the transcription factor activity under varying conditions, and 3) isolate the pathways and monitor the effects of the cytokines on each of pathway. This approach, which is based on Systems Biology, is about putting together rather than taking apart, integration rather than reduction. Thus, once we have researched the above three factors, we can put them together to hypothesize and test the cross-talk.