Cholangiocyte secretion of chemokines in experimental biliary atresia

Mubeen Jafri, Bryan Donnelly, Alex Bondoc, Steven Allen, Greg Tiao

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)500-507
Number of pages8
JournalJournal of Pediatric Surgery
Volume44
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

Fingerprint

Biliary Atresia
Chemokines
Rotavirus
Rotavirus Infections
Chemokine CXCL2
Extrahepatic Bile Ducts
Chemokine CCL2
Cholestasis
Serum-Free Culture Media
Biliary Tract
Virus Diseases
Bile Ducts
Epithelial Cells
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cell Line
Polymerase Chain Reaction
Injections

Keywords

  • Biliary atresia
  • Chemokines
  • Cholangiocyte
  • Rotavirus

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Cholangiocyte secretion of chemokines in experimental biliary atresia. / Jafri, Mubeen; Donnelly, Bryan; Bondoc, Alex; Allen, Steven; Tiao, Greg.

In: Journal of Pediatric Surgery, Vol. 44, No. 3, 03.2009, p. 500-507.

Research output: Contribution to journalArticle

Jafri, Mubeen ; Donnelly, Bryan ; Bondoc, Alex ; Allen, Steven ; Tiao, Greg. / Cholangiocyte secretion of chemokines in experimental biliary atresia. In: Journal of Pediatric Surgery. 2009 ; Vol. 44, No. 3. pp. 500-507.
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