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ANTIMICROBIAL PEPTIDES AND INTERSTITIAL CYSTITIS

In 1929, Drs Peterson and Hager first used the term ‘Interstitial Cystitis’ (IC) to describe the painful bladder condition that is all too familiar to over 180,000 women in the UK today. Unfortunately, 80-years later our understanding of what causes this problem remains very limited which in turn hampers development of effective treatments. To try to increase our knowledge of possible problems that may set off IC, our research group at Newcastle University will look at the influence of natural antibiotics in a project partly funded by the COB Foundation.

Gaps in the GAG layer
What is known in IC is that there appears to be a problem in the protective layers of the bladder. This is thought to be due to a defect in the ‘glycosaminoglycan’ (GAG) layer which protects the surface of the bladder from harmful constituents of urine e.g. waste products coming down from the kidney or bacterial bugs coming up the urethra. In a sense the GAG layer is like a protective paint; just as unpainted wood is susceptible to the elements, the bladder is more susceptible to harmful urinary contents when the GAG layer is absent. Unfortunately, no-one really knows how the GAG layer gets damaged in the first place.

Importance of Past Infections
Interestingly, it is known that during a urinary infection (UTI), bacterial bugs temporarily damage the protective layers of the bladder and can even get into the cells lining the bladder. It is possible that people with IC have some defect in the way their bladder defends against infection and as a result bacteria are able to cause irreversible damage to their protective GAG layer leading to chronic painful cystitis even when all the bugs have been removed by the body's defences.

Natural ‘Bug-Buster’ Chemicals
Crohn’s disease is an inflammatory condition of the gut which has many similarities with IC including defects in the GAG layer. Recently scientists have found that the lining cells of the gut from people with Crohn’s disease have much lower than normal levels of natural antibiotics called antimicrobial peptides (AMPs). These are tiny chemicals made by cells lining different parts of the body such as the gut, bladder, skin, lungs and eyes which act as natural antibiotics destroying bacteria before they have a chance to invade - ‘bug-busters’.

Our Research Question
So the question we have set ourselves is if these AMPs are reduced in people with problems with the gut protective layer, maybe the same is true in the bladder? To find the answer we will investigate whether the lining cells of the bladder from women with IC have less natural antibiotic activity compared to women without painful bladder symptoms. We will also test the activity in the cells lining the vagina since this is often where urinary infection starts. The study is supported by the COB Foundation and the Wellcome Trust and the flow chart shows how the study will run.

What we Need to Do
We will analyse the samples obtained to compare natural antibiotic activity in women with and without painful bladders to see if there is a difference in their amount, type or function of the bug-busting natural chemicals. To date, 12 ‘normal’ volunteers have been recruited and we will now start asking our patients with IC.

Our Hopes
This work is very exciting and could open up entirely new avenues of research in IC. The research team would like to express our thanks for the funding support from the COB Foundation. We hope that your support will allow us to make progress towards finding the underlying causes of IC and lead us along the path to effective treatment.

The Research Team
Researchers (left to right): Ased Ali, Marcelo Lanz, Claire Townes, Judith Hall and Rob Pickard from the Institute of Cellular Medicine and the Institute for Cell and Molecular Biosciences, Newcastle University.