TY - JOUR
T1 - High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas
AU - Sanlioglu, Ahter Dilsad
AU - Dirice, Ercument
AU - Elpek, Ozlem
AU - Korcum, Aylin Fidan
AU - Balci, Mustafa Kemal
AU - Omer, Abdulkadir
AU - Griffith, Thomas S.
AU - Sanlioglu, Salih
PY - 2008/5
Y1 - 2008/5
N2 - OBJECTIVES: Type 1 diabetes (T1D) has been characterized by the T cell-mediated destruction of pancreatic β 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.
AB - OBJECTIVES: Type 1 diabetes (T1D) has been characterized by the T cell-mediated destruction of pancreatic β 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.
KW - Death-decoy receptors
KW - Langerhans islets
KW - Pancreas
KW - TRAIL
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U2 - 10.1097/MPA.0b013e318158a4e5
DO - 10.1097/MPA.0b013e318158a4e5
M3 - Article
C2 - 18437085
AN - SCOPUS:42549135360
SN - 0885-3177
VL - 36
SP - 385
EP - 393
JO - Pancreas
JF - Pancreas
IS - 4
ER -