Jan. 12 /PRNewswire/ -- Expanding on the success of its program to mine the human genome for novel protein therapeutics, researchers at ZymoGenetics, Inc. have identified a new member of the interleukin family of proteins. Results published today in the journal Cell suggest that the molecule, designated Interleukin 20 (IL-20), and its associated receptor may be implicated in the development of psoriasis.
Scientists at ZymoGenetics discovered the human gene coding for IL-20, which belongs to a class of cytokines responsible for regulating a wide variety of cellular processes in both healthy and diseased tissues. ZymoGenetics scientists further characterized the interaction between the IL-20 protein and a cell-surface receptor composed of two subunits, named IL-20R alpha and IL-20R beta, that are present in human skin cells.
``In one of our first clues to the biology of this protein, we observed a striking similarity between the skin of mice that overproduce IL-20 and human psoriatic skin,'' said Frank Collins, Ph.D., Senior Vice President of Research at ZymoGenetics. ``Our finding that both IL-20 receptor subunits are expressed in elevated levels in psoriatic skin further supports the idea that IL-20 is involved in this disease.'' He added, ``ZymoGenetics is currently conducting animal studies to determine if inhibition of the IL-20 ligand will have a therapeutic role in regulating the pathogenesis of psoriasis.''
``The discovery of IL-20 demonstrates our ability to use bioinformatics to identify novel genes that code for proteins with therapeutic implications,'' said Bruce L. A. Carter, Ph.D., President and Chief Executive Officer of ZymoGenetics. ``Also critical to our discovery strategy is ZymoGenetics' expertise in pairing the binding between ligands and receptors, as we did with IL-20 and the two IL-20 receptor subunits, to elucidate the biology of a system. Knowing the receptor is like having a 'key' to unlock the biology of a novel protein.''
Dr. Carter noted that today's research is another example of ZymoGenetics' ability to pair ligands and receptors. It follows the company's recent discovery, published in the November 2, 2000 issue of Nature, of the IL-21 ligand/receptor pair and its potential role in cancer therapy.
Potential Role of IL-20 in Psoriasis
In today's paper, ZymoGenetics researchers describe for the first time the identification of IL-20 ligand and the interaction of IL-20 with its two receptor subunits, IL-20R alpha and IL-20R beta. Three key findings led the company's team to identify a potential connection between IL-20 and development of psoriasis:
* Studies with IL-20 demonstrated that it stimulates the activation of
human keratinocytes, cells present in the outer most layer of the skin,
when the cells were grown in laboratory culture.
* In transgenic mice genetically engineered to overproduce IL-20 within
their bodies, ZymoGenetics scientists observed that the mice developed
skin similar to psoriatic skin lesions in humans.
* Analysis of human skin tissues for the presence of the two receptor
subunits for IL-20 demonstrated that both molecules are present at very
low levels in normal skin and present at much higher levels in psoriatic skin.
Authors on the Cell article, titled ``Interleukin 20: Discovery, Receptor Identification and Role in Epidermal Function,'' include researchers from both ZymoGenetics and the University of Washington. Senior authors on the paper are Yasmin Chandrasekher, Ph.D., Senior Scientist, and Hal Blumberg, Ph.D., Senior Scientist, both of ZymoGenetics... |
