Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis

Xian Ming Chen, Susan A. Levine, Patrick L. Splinter, Pamela S. Tietz, Amanda L. Ganong, Christian Jobin, Gregory James Gores, Carlos V. Paya, Nicholas F La Russo

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Background & Aims: Our previous studies have shown that Cryptosporidium parvum induces biliary epithelial cell apoptosis in vivo and causes apoptosis in bystander uninfected biliary epithelia in vitro. We analyzed C. parvum-induced nuclear factor kappa B (NF-κB) activation in human biliary epithelial cells and assessed its relevance to epithelial cell apoptosis. Methods: In vitro models of cryptosporidial infection using a human biliary epithelial cell line were used to assay C. parvum-induced NF-κB activation and associated apoptosis. Results: Degradation of IκB and nuclear translocation of the NF-κB family of proteins (p65 and p50) were observed in the biliary epithelial cell cultures directly exposed to the parasite. Activation of NF-κB was found only in directly infected cells (but not in bystander uninfected cells). A time-dependent secretion of a known NF-κB gene product, interleukin 8, from infected cell cultures was detected. C. parvum-induced biliary epithelial cell apoptosis was limited to bystander uninfected cells. In contrast, inhibition of NF-κB activation resulted in apoptosis in directly infected cells and significantly enhanced C. parvum-induced apoptosis in bystander uninfected cells. Conclusions: These observations support the concept that, while C. parvum triggers host cell apoptosis in bystander uninfected biliary epithelial cells, which may limit spread of the infection, it directly activates the NF-κB/IκB system in infected biliary epithelia thus protecting infected cells from death and facilitating parasite survival and propagation.

Original languageEnglish (US)
Pages (from-to)1774-1783
Number of pages10
JournalGastroenterology
Volume120
Issue number7
StatePublished - 2001
Externally publishedYes

Fingerprint

Cryptosporidium parvum
NF-kappa B
Epithelium
Epithelial Cells
Apoptosis
Parasites
Cell Culture Techniques
Infection
Interleukin-8
Cell Death
Cell Line

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Chen, X. M., Levine, S. A., Splinter, P. L., Tietz, P. S., Ganong, A. L., Jobin, C., ... La Russo, N. F. (2001). Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis. Gastroenterology, 120(7), 1774-1783.

Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis. / Chen, Xian Ming; Levine, Susan A.; Splinter, Patrick L.; Tietz, Pamela S.; Ganong, Amanda L.; Jobin, Christian; Gores, Gregory James; Paya, Carlos V.; La Russo, Nicholas F.

In: Gastroenterology, Vol. 120, No. 7, 2001, p. 1774-1783.

Research output: Contribution to journalArticle

Chen, XM, Levine, SA, Splinter, PL, Tietz, PS, Ganong, AL, Jobin, C, Gores, GJ, Paya, CV & La Russo, NF 2001, 'Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis', Gastroenterology, vol. 120, no. 7, pp. 1774-1783.
Chen XM, Levine SA, Splinter PL, Tietz PS, Ganong AL, Jobin C et al. Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis. Gastroenterology. 2001;120(7):1774-1783.
Chen, Xian Ming ; Levine, Susan A. ; Splinter, Patrick L. ; Tietz, Pamela S. ; Ganong, Amanda L. ; Jobin, Christian ; Gores, Gregory James ; Paya, Carlos V. ; La Russo, Nicholas F. / Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis. In: Gastroenterology. 2001 ; Vol. 120, No. 7. pp. 1774-1783.
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AU - Ganong, Amanda L.

AU - Jobin, Christian

AU - Gores, Gregory James

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AU - La Russo, Nicholas F

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N2 - Background & Aims: Our previous studies have shown that Cryptosporidium parvum induces biliary epithelial cell apoptosis in vivo and causes apoptosis in bystander uninfected biliary epithelia in vitro. We analyzed C. parvum-induced nuclear factor kappa B (NF-κB) activation in human biliary epithelial cells and assessed its relevance to epithelial cell apoptosis. Methods: In vitro models of cryptosporidial infection using a human biliary epithelial cell line were used to assay C. parvum-induced NF-κB activation and associated apoptosis. Results: Degradation of IκB and nuclear translocation of the NF-κB family of proteins (p65 and p50) were observed in the biliary epithelial cell cultures directly exposed to the parasite. Activation of NF-κB was found only in directly infected cells (but not in bystander uninfected cells). A time-dependent secretion of a known NF-κB gene product, interleukin 8, from infected cell cultures was detected. C. parvum-induced biliary epithelial cell apoptosis was limited to bystander uninfected cells. In contrast, inhibition of NF-κB activation resulted in apoptosis in directly infected cells and significantly enhanced C. parvum-induced apoptosis in bystander uninfected cells. Conclusions: These observations support the concept that, while C. parvum triggers host cell apoptosis in bystander uninfected biliary epithelial cells, which may limit spread of the infection, it directly activates the NF-κB/IκB system in infected biliary epithelia thus protecting infected cells from death and facilitating parasite survival and propagation.

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