Re: How ulcerative colitis works

[Guest guest]

Thanks for sharing , I'll see if there's a publication associated with

this study on PubMed.

>

> This article was posted on the Yahoo PSC Support group I belong to for

> my husband's autoimmune liver disease (which causes Crohns or UC, 75% of

> the time).

>

> Enzyme Involved In Inflammatory Bowel Disease Discovered At Penn State

> College Of Medicine

> Main Category: Crohn's

> Also Included In: Irritable-Bowel Syndrome; Immune System / Vaccines;

> Biology / Biochemistry

> Article Date: 03 Jun 2009 - 5:00 PDT

>

> Researchers at Penn State College of Medicine, working with biochemists,

> geneticists and clinicians at the University of Bern, Switzerland and in

> the United Kingdom, have discovered an enzyme that has a key role in

> inflammatory bowel disease (IBD). The team, co-led by Judith Bond,

> Ph.D., Distinguished Professor and Chair of Biochemistry and Molecular

> Biology at Penn State College of Medicine, and Lottaz, Department

> of Rheumatology and Clinical Immunology at the University of Bern,

> Switzerland, could potentially lead to therapies to help the

> half-a-million Americans affected by ulcerative colitis and Crohn's

> disease, collectively referred to as IBD.

>

> The enzyme, coded for by the MEP1A gene, is a zinc-containing

> metalloprotease called meprin, and is abundant in the intestine. A

> protease is an enzyme that breaks down proteins in the body.

>

> Researchers at Penn State College of Medicine studied the role of meprin

> in IBD using genetically altered mice lacking the ability to produce the

> enzyme in collaboration with colleagues in Switzerland who studied the

> enzyme in IBD patients. Meprin is abundant in the latter part of the

> small intestine, or terminal ileum, and is also present in the large

> intestine at a lower level. The European researchers found an alteration

> in the meprin gene that correlated with IBD. They then compared the

> levels of meprin in affected and unaffected sections of colons from IBD

> patients and from healthy people. The amount of enzyme in the IBD

> patient's inflamed colon was significantly lower than that in normal

> colon sections. The researchers concluded that their findings strongly

> correlate the severity of inflammation associated with both Crohn's

> disease and ulcerative colitis with low meprin levels.

>

> " This discovery is a major advance in understanding the genetic control

> of inflammation, and of ulcerative colitis and Crohn's disease in

> particular, " Bond said. She discovered meprin more than 25 years ago

> while at the Medical College of Virginia Commonwealth University. Since

> then, she has studied the structure and activities of the meprins and

> has located the genes for the subunits in both the mouse and human

> chromosomes. After coming to Penn State Hershey in 1992, her studies

> have focused on the biomedical significance of the meprin proteases.

> With colleagues from the National Institutes of Health, she found a

> linkage between the meprin gene and vulnerability to diabetic

> nephropathy in Pima Indians in the southwestern United States.

>

> " These types of transitional research that provide sound basic

> understanding of a disease process, coupled with detailed examination

> and critical interpretation of clinical findings, are dependent upon

> sustained collaborations based upon trust and respect, " Bond said.

> Before this international effort, she teamed up with kidney specialists

> at Albert Einstein College of Medicine in New York and with W.

> Reeves, M.D., at Penn State Hershey to demonstrate that meprin

> influences the outcome of acute renal failure in mice.

>

> The Penn State researchers used a mouse model of IBD, replicating

> inflammation in the intestine like that in human ulcerative colitis.

> Mice lacking meprin had more severe intestinal damage after drinking a

> solution to induce inflammation, than did the wild-type mice that have

> meprin. These results indicate that meprin reduces the level of

> inflammation in the injured intestine.

>

> In the mouse model, it is possible to make detailed measurements on a

> number of consequences of inflammation. Nitric oxide in the blood is an

> important host defense against bacterial infection, but its power as an

> oxidant also damages host tissue. A nitric oxide level in the blood of

> mice lacking meprin was much higher than the level in wild-type mice.

> The Penn State team also discovered that meprin is able to activate an

> inflammatory serum factor produced by white blood cells, and this factor

> is elevated in both the mouse model of IBD and in humans with active

> IBD. Bond explained, " The defect in the human meprin gene most

> associated with ulcerative colitis is in a region that regulates

> production of the meprin protein. "

>

> The researchers concluded that a particular defect in the MEP1A gene is

> an indicator of vulnerability to IBD, particularly ulcerative colitis.

> The association of the meprin gene with Crohn's disease remains to be

> characterized but disruption of the meprin gene affects the severity of

> both ulcerative colitis and Crohn's disease. Bond summarized the

> findings by saying, " There's the possibility of predicting who will be

> susceptible to IBD, and diagnosing the disease with this information. If

> we could increase meprin production, or replace it with an equivalent

> enzyme, there are therapeutic possibilities. More studies are needed to

> understand how meprin influences inflammation, but this is the first

> association of meprin levels as a key factor in the severity of IBD. "

>

> Other Penn State College of Medicine researchers include Sanjita

> Banerjee and Gail L. Matters, Ph.D., in the Department of Biochemistry

> and Molecular Biology, and Leo Fitzpatrick, Ph.D., in the Department of

> Pharmacology.

>

> Source:

> G. Solovey

> Penn State Hershey Medical Center, Penn State College of Medicine

>

> --

> Hussey

> Wife of Fred, PSC 03/04, UC 0306, SCD 04/09 (started in the hospital!!Talk

about TOUGH!

>