High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas.
OBJECTIVE
Type 1 diabetes (T1D) has been characterized by the T cell-mediated destruction of pancreatic beta cells. Although various members of the tumor necrosis factor (TNF) family, such as Fas ligand or TNF, have recently been implicated in the development of T1D, the lack of TNF-related apoptosis-inducing ligand (TRAIL) expression or function facilitates the onset of T1D. Thus, the goal of the present study was to investigate the expression profiles of TRAIL and its receptors in human pancreas.


METHODS
Pancreata of 31 patients were analyzed by immunohistochemistry using antibodies developed against TRAIL and its receptors. Apoptosis was confirmed by Annexin V-fluorescein isothiocyanate binding and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assays.


RESULTS
Acinar cells displayed high levels of TRAIL and death receptor 4, but only low levels of death receptor 5. In contrast, only TRAIL and TRAIL decoy receptors (DcR1, DcR2) were detected in ductal cells. Similarly, Langerhans islets expressed only TRAIL and TRAIL decoy receptor. High levels of TRAIL expression in pancreas correlated with increased number of apoptotic cells.


CONCLUSIONS
Although the expression of TRAIL decoy receptors might be necessary for defense from TRAIL-induced apoptosis, high levels of TRAIL may provide protection for Langerhans islets from the immunological attack of cytotoxic T cells.
Sanlioglu
Ahter Dilsad
AD
Human Gene Therapy Unit, Departments of Medical Biology and Genetics, Akdeniz University, Faculty of Medicine, Antalya, Turkey. sanlioglu@akdeniz.edu.tr
Dirice
Ercument
E
Elpek
Ozlem
O
Korcum
Aylin Fidan
AF
Balci
Mustafa Kemal
MK
Omer
Abdulkadir
A
Griffith
Thomas S
TS
Sanlioglu
Salih
S
D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology* / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis; D012016:Reference Values; D013274:Stomach Neoplasms / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha