Induction of the chemokine interferon-gamma-inducible protein-10 in human pancreatic islets during enterovirus infection.
OBJECTIVE
Enterovirus infections have long been suspected to be environmental factors that may cause type 1 diabetes, but the pathways leading from infection to beta cell destruction are still unknown. We therefore examined whether enterovirus infection of human islets leads to upregulation of interferon-gamma-inducible protein (IP-10, now known as chemokine [C-X-C motif] ligand 10 [CXCL10]), a chemokine important for the induction of insulitis.


METHODS
Isolated human islets were infected with three different strains of Coxsackie B4 virus. IP-10 expression and secretion from the infected human islets were then measured using RT-PCR and ELISA at several time points.


RESULTS
IP-10 was clearly upregulated in and secreted from human islets during enterovirus infection. This was demonstrated with three different strains of Coxsackie B4 virus, two of which are lytic to islets and one which is non-lytic and can establish a persistent infection in human islets.


CONCLUSIONS
We propose that enterovirus-induced upregulation of IP-10 during infection of the islets in vivo is the first step towards destructive insulitis. Our findings support the idea that enterovirus infection triggers immune-mediated beta cell destruction, and for the first time suggest a possible mechanism behind enterovirus-induced diabetes.
Berg
A-K
AK
Department of Women's and Children's Health, Uppsala University, Akademiska Sjukhuset, ing 95/96, SE-751 85 Uppsala, Sweden.
Korsgren
O
O
Frisk
G
G
D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D002102:Cadaver; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D029822:Enterovirus B, Human; D004769:Enterovirus Infections / Q000235:genetics / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
D000199:Actins; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012333:RNA, Messenger