TRAIL and its receptors in the colonic epithelium: a putative role in the defense of viral infections.
OBJECTIVE
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family and induces apoptosis by cross-linking either of the 2 TRAIL receptors containing a death domain (TRAIL-R1 or TRAIL-R2). TRAIL-R3 and TRAIL-R4 are receptors that do not transmit an apoptotic signal. The aim of this study was to investigate the expression and function of TRAIL and its receptors in normal colonic epithelium.


METHODS
TRAIL and TRAIL receptor expression was studied by reverse-transcriptase polymerase chain reaction and immunohistochemistry. TRAIL sensitivity of epithelial cells was determined in vitro.


RESULTS
Normal colonic epithelial cells express TRAIL, TRAIL-R1, TRAIL-R2, and TRAIL-R4. Interestingly, TRAIL and TRAIL-R2 are coexpressed mostly in the luminal surface epithelium. Despite the expression of apoptosis-mediating TRAIL receptors, the normal colonic crypt epithelium is completely resistant to TRAIL-induced apoptosis in vitro. Using an infection model with restricted human cytomegalovirus gene expression or productive adenovirus infection in the colon carcinoma cell line Caco-2, we show that TRAIL sensitivity of colonic epithelial cells is induced on virus infection along with an up-regulation of TRAIL-R1 and TRAIL-R2 on the cell surface.


CONCLUSIONS
We conclude that the TRAIL system may play a role in the early elimination of virus-infected epithelial cells in the normal gut.
Sträter
Jörn
J
Department of Pathology, University of Ulm, Ulm, Germany. joern.straeter@medizin.uni-ulm.de
Walczak
Henning
H
Pukrop
Tanja
T
Von Müller
Lutz
L
Hasel
Cornelia
C
Kornmann
Marko
M
Mertens
Thomas
T
Möller
Peter
P
D000257:Adenoviridae Infections / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D018938:Caco-2 Cells; D003106:Colon / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D003586:Cytomegalovirus Infections / Q000473:pathology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha