Submitted on March 22, 2005
Accepted on July 25, 2005
IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression
Stephan Brand1*, Florian Beigel1, Torsten Olszak1, Kathrin Zitzmann1, Soeren T. Eichhorst1, Jan-Michel Otte2, Joachim Diebold3, Helmut Diepolder1, Barbara Adler4, Christoph J. Auernhammer1, Burkhard Goke1, and Julia Dambacher1
1 Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Munich, Germany
2 Department of Medicine I, St. Josef-Hospital, Ruhr-University, Bochum, Germany
3 Institute of Pathology, University-Hospital Munich-Grosshadern, University of Munich, Munich, Germany
4 Max von Pettenkofer-Institute, University of Munich, Munich, Germany
* To whom correspondence should be addressed. E-mail: stephan.brand{at}med.uni-muenchen.de.
Human cytomegaly virus (HCMV) is a major cause of morbidity and mortality in
immunocompromised individuals. Recently, a novel group of cytokines (IL-28A/B and IL-29,
also termed interferon/IFN-
s) was described. Here, we demonstrate that intestinal epithelial
cell (IEC) lines as well as murine and human colonic tissue express the IFN- receptor
subunits IL-28R and IL-10R2. IL-28A and IL-29 binding to their receptor complex activates
ERK-1/2 and SAPK/JNK MAP kinases, and Akt resulting in increased IL-8 protein
expression. IFN-s also induce phosphorylation of STAT1 and significantly increase the
mRNA expression of SOCS-3 and the antiviral proteins MxA and 2',5'-OAS. These signals
result in an up to 83% reduction of cells positive for HCMV immediate early protein after
HCMV infection. In mice, IL-28A mRNA expression is upregulated following infection with
murine cytomegaly virus (MCMV) in vivo. Both, IL-28A and IL-29 decrease significantly
cell proliferation but have no effect on Fas induced apoptosis. In conclusion, intestinal
epithelial cells express functional receptors for IFN-s, which mediate antiviral and
antiproliferative signals in intestinal epithelial cells suggesting a potential for therapeutic use
in certain viral infections and as (antiproliferative) anti-cancer therapy.
