Investigating the Interactions between Cytokines Interleukin-1 and Interleukin-6

The purpose of this research project is to study the signaling pathways of the \ninflammatory cytokines - Interleukin-1 (IL-1) and Interleukin-6 (IL-6) - and investigate \nany "cross-talk" between the two. IL-6 plays a central role in the Non-Alcoholic Fatty \nLiver Disease (NAFLD) and we hypothesize that the progression of NAFLD is caused \nby the imbalance in downstream transcription factor activity of IL-1 and IL-6. Thus, \ninvestigating the possible cross-talk would be beneficial in assessing this imbalance. \nAccording to the previous work done by the research group, green fluorescent protein \n(GFP) reporter plasmids with STAT3 and C/EBPB transcription factor binding \nsequences were transfected into human hepatocarcinoma (HepG2) cells. Once they were \nstimulated with cytokines IL-6 or IL-10, they were analyzed with fluorescence \nmicroscopy which showed that the transcription factors STAT3 and C/EBPB were \nactivated leading to a corresponding expression of GFP. This research project will be \nfocused on the dynamics of IL-6 and the effects of IL-1 (instead of IL-10) on it. IL-1 and \nIL-6 are both involved in many inflammatory responses of the body and by having a \ndeeper understanding about their pathways to initiation of the inflammatory responses and any interconnections will help us model a feedback system to control the response. \nThe findings will assist in finding a therapeutic approach to mitigate various \ninflammatory diseases where IL-1 and IL-6 play a major role in (e.g. NAFLD). In \naddition, these results will also be useful in bioengineering. Inflammatory response of \nthe body towards any bioengineered implants mediated by these cytokines could be \ncontrolled on a molecular level. Thus, instead of wasting thousands of dollars on coming \nup with a new design, bioengineers can manipulate the body?s response and use the \ndevice that was formerly rejected by the body. Research will be conducted to 1) quantify \nthe transcription factor activity, 2) study the dynamics of the transcription factor activity \nunder varying conditions, and 3) isolate the pathways and monitor the effects of the \ncytokines on each of pathway. This approach, which is based on Systems Biology, is \nabout putting together rather than taking apart, integration rather than reduction. Thus, \nonce we have researched the above three factors, we can put them together to \nhypothesize and test the cross-talk.