NF-kB activation in myeloid cells
Research type
Research Study
Full title
An investigation into gene regulation in blood-derived inflammatory cells from chronic inflammatory environments.
IRAS ID
188513
Contact name
Kimberly A Mace
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
1 years, 9 months, 31 days
Research summary
Chronic, low-level inflammation is a hallmark of diabetes and its complications, including the diabetic chronic wound. During wound healing, white blood cells are recruited to the wound from the bloodstream, where they contribute to the healing process before then dying or leaving the wound. However, in diabetes, the recruited cells are dysfunctional and remain in the wound for a prolonged period of time, where they contribute to chronic inflammation and a failure of the wound to heal.
We have shown using diabetic mice that even before white blood cells reach the wound, diabetes induces changes to their gene expression patterns and capacity to mature and respond to activation signals. In particular, white blood cells from diabetic mice show a heightened response to inflammatory stimuli that may reflect underlying changes to the chromatin into which genes are packaged, and which controls gene activation and repression. Preliminary evidence also suggests that the NF-κB pathway, a crucial part of the inflammatory cascade that is activated in response to inflammatory signals received by cells, may be dysregulated in diabetic white blood cells.
In this study, we aim to determine whether the same changes that we see in white blood cells from diabetic mice are also seen in white blood cells from individuals with diabetes. In particular, we will characterise cells’ response to inflammatory signals, with focus on the NF-κB pathway and on the changes to chromatin that may underpin the altered behaviour of diabetic white blood cells. Understanding of the mechanisms by which chronic inflammation occurs will allow us to develop strategies for its control and may eventually lead to treatments for the complications of diabetes.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
16/YH/0415
Date of REC Opinion
23 Sep 2016
REC opinion
Favourable Opinion