Cholangiocyte secretion of chemokines in experimental biliary atresia.
Biliary atresia (BA) is a disease of the newborn that results in obstruction of the biliary tree. The cause of BA remains unknown; however, recent studies using the murine model of biliary atresia have found that rotavirus infection of the biliary epithelial cell (cholangiocyte) triggers an inflammatory response. We hypothesized that rotavirus infection of cholangiocytes results in the release of chemokines, important mediators of the host immune response.


METHODS
In vivo, Balb/c pups were injected with rhesus rotavirus (RRV) or saline, and, their extrahepatic bile ducts were microdissected 2, 5, 7, and 14 days after injection. Next, an immortalized cholangiocyte cell line (mCl) was incubated with RRV or serum-free media. Qualitative and quantitative chemokine assessment was performed using enzyme-linked immunosorbent assay, polymerase chain reaction, and immunohistochemistry.


RESULTS
In vivo, increased levels of the chemokines macrophage inflammatory protein 2, monocyte chemotactic protein 1, KC and Regulated upon Activation, Normal T Expressed and Secreted were found in RRV-infected murine bile ducts. In vitro, infected mCl cells produced increasing amounts of these same chemokines in relation to dose and time.


CONCLUSIONS
These novel results suggest that chemokine expression by RRV-infected cholangiocytes may trigger a host inflammatory process that causes bile duct obstruction. Understanding how viral infection initiates this response may shed light on the pathogenesis of biliary atresia.
Jafri
Mubeen
M
Department of Pediatric and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Donnelly
Bryan
B
Bondoc
Alex
A
Allen
Steven
S
Tiao
Greg
G
D000818:Animals; D000831:Animals, Newborn; D017734:Bile Ducts, Extrahepatic / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D001656:Biliary Atresia / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D012401:Rotavirus
C499538:Ccl17 protein, mouse; C491768:Ccl2 protein, mouse; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse