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Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways.
Liver Int. 2006 May; 26(4):467-76.LI

Abstract

BACKGROUND

Human intrahepatic biliary epithelial cells (HIBECs) may play active roles in both the innate and adaptive immune responses. Little is known, however, about the role of toll-like receptors (TLRs) on HIBECs in inflammatory cholangiopathies.

METHODS

The expression of TLR1-9 and the biological responses to their ligands, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), were studied in cultured HIBECs by reverse transcription-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay.

RESULTS

HIBECs constitutively expressed transcripts encoding TLR1-6 and 9, as well as myeloid differentiation factor 88 (MyD88), MD2, and CD14. Stimulation of HIBECs with LPS resulted in translocation of NF-kappaB subunits from the cytoplasmic to the nuclear fraction, followed by increased secretion of a variety of chemokines/cytokines, including interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and IL-6. Treatment with BAY11-7082 efficiently inhibited the LPS-induced transcription and secretion of these chemokines/cytokines. In HIBECs, the mitogen-activated protein kinases (MAPKs) were also activated by LPS stimulation. These results indicated that LPS activates HIBECs via a TLR4-MyD88-dependent pathway. Stimulation of HIBECs with LTA induced the secretion of a similar profile of cytokines/chemokines via a TLR2-MyD88-dependent pathway.

CONCLUSIONS

In HIBECs, at least TLR2 and 4 are capable of mediating innate immune system function in vitro. This result, in conjunction with our recent finding that TLR4 expression is increased in biliary epithelial cells in primary biliary cirrhosis, suggests the involvement of TLRs in the development of chronic inflammatory cholangiopathies.

Authors+Show Affiliations

Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Nagasaki, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16629651

Citation

Yokoyama, Terufumi, et al. "Human Intrahepatic Biliary Epithelial Cells Function in Innate Immunity By Producing IL-6 and IL-8 Via the TLR4-NF-kappaB and -MAPK Signaling Pathways." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 26, no. 4, 2006, pp. 467-76.
Yokoyama T, Komori A, Nakamura M, et al. Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways. Liver Int. 2006;26(4):467-76.
Yokoyama, T., Komori, A., Nakamura, M., Takii, Y., Kamihira, T., Shimoda, S., Mori, T., Fujiwara, S., Koyabu, M., Taniguchi, K., Fujioka, H., Migita, K., Yatsuhashi, H., & Ishibashi, H. (2006). Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways. Liver International : Official Journal of the International Association for the Study of the Liver, 26(4), 467-76.
Yokoyama T, et al. Human Intrahepatic Biliary Epithelial Cells Function in Innate Immunity By Producing IL-6 and IL-8 Via the TLR4-NF-kappaB and -MAPK Signaling Pathways. Liver Int. 2006;26(4):467-76. PubMed PMID: 16629651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways. AU - Yokoyama,Terufumi, AU - Komori,Atsumasa, AU - Nakamura,Minoru, AU - Takii,Yasushi, AU - Kamihira,Takashi, AU - Shimoda,Shinji, AU - Mori,Tsuyoshi, AU - Fujiwara,Shinsuke, AU - Koyabu,Makiko, AU - Taniguchi,Ken, AU - Fujioka,Hikaru, AU - Migita,Kiyoshi, AU - Yatsuhashi,Hiroshi, AU - Ishibashi,Hiromi, PY - 2006/4/25/pubmed PY - 2006/9/16/medline PY - 2006/4/25/entrez SP - 467 EP - 76 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int VL - 26 IS - 4 N2 - BACKGROUND: Human intrahepatic biliary epithelial cells (HIBECs) may play active roles in both the innate and adaptive immune responses. Little is known, however, about the role of toll-like receptors (TLRs) on HIBECs in inflammatory cholangiopathies. METHODS: The expression of TLR1-9 and the biological responses to their ligands, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), were studied in cultured HIBECs by reverse transcription-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. RESULTS: HIBECs constitutively expressed transcripts encoding TLR1-6 and 9, as well as myeloid differentiation factor 88 (MyD88), MD2, and CD14. Stimulation of HIBECs with LPS resulted in translocation of NF-kappaB subunits from the cytoplasmic to the nuclear fraction, followed by increased secretion of a variety of chemokines/cytokines, including interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and IL-6. Treatment with BAY11-7082 efficiently inhibited the LPS-induced transcription and secretion of these chemokines/cytokines. In HIBECs, the mitogen-activated protein kinases (MAPKs) were also activated by LPS stimulation. These results indicated that LPS activates HIBECs via a TLR4-MyD88-dependent pathway. Stimulation of HIBECs with LTA induced the secretion of a similar profile of cytokines/chemokines via a TLR2-MyD88-dependent pathway. CONCLUSIONS: In HIBECs, at least TLR2 and 4 are capable of mediating innate immune system function in vitro. This result, in conjunction with our recent finding that TLR4 expression is increased in biliary epithelial cells in primary biliary cirrhosis, suggests the involvement of TLRs in the development of chronic inflammatory cholangiopathies. SN - 1478-3223 UR - https://www.unboundmedicine.com/medline/citation/16629651/Human_intrahepatic_biliary_epithelial_cells_function_in_innate_immunity_by_producing_IL_6_and_IL_8_via_the_TLR4_NF_kappaB_and__MAPK_signaling_pathways_ L2 - https://doi.org/10.1111/j.1478-3231.2006.01254.x DB - PRIME DP - Unbound Medicine ER -