Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid

Yong Han Paik, Kwan Sik Lee, Hyun Jin Lee, Kyung Min Yang, Se Jun Lee, Dong Ki Lee, Kwang Hyub Han, Chae Yoon Chon, Sang In Lee, Young Myoung Moon, David A. Brenner

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62 Citations (Scopus)

Abstract

Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic acid (LTA) are potent stimulators of innate inflammatory responses. We previously reported that lipopolysaccharide (LPS), a major biologically active agent of gram-negative bacteria, induces a proinflammatory response via the Toll-like receptor (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of proinflammatory action by PGN and LTA in activated human HSCs. Following treatment with either TNF-α or IL-1β, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-κB activation was assessed by NF-κB-driven luciferase assay and electrophoretic mobility shift assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA. Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA signaling. TNF-α and IL-1β significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-κB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-α or IL-1β augmented NF-κB activation and IL-8 production in response to PGN or LTA. Both PGN- and LTA-induced NF-κB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-α or IL-1β primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.

Original languageEnglish
Pages (from-to)676-686
Number of pages11
JournalLaboratory Investigation
Volume86
Issue number7
DOIs
Publication statusPublished - 2006 Jul 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Paik, Y. H., Lee, K. S., Lee, H. J., Yang, K. M., Lee, S. J., Lee, D. K., Han, K. H., Chon, C. Y., Lee, S. I., Moon, Y. M., & Brenner, D. A. (2006). Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid. Laboratory Investigation, 86(7), 676-686. https://doi.org/10.1038/labinvest.3700422