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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 
 LABORATORY INVESTIGATION, Vol.86(7) : 676-686, 2006 
Journal Title
Issue Date
Adenoviridae/genetics ; Biomarkers/metabolism ; Cell Culture Techniques ; Cell Line, Transformed ; Cytokines/immunology* ; Fibrosis/chemically induced ; Fibrosis/pathology ; Genes, Reporter ; Hepatocytes/cytology ; Hepatocytes/physiology* ; Humans ; Inflammation/chemically induced ; Inflammation/pathology ; Interleukin-1/immunology ; Interleukin-8/biosynthesis ; Lipopolysaccharide Receptors/immunology ; Lipopolysaccharides/immunology* ; Liver/cytology* ; Luciferases/immunology ; NF-kappa B/immunology ; Peptidoglycan/immunology* ; Teichoic Acids/immunology* ; Toll-Like Receptor 2/immunology ; Tumor Necrosis Factor-alpha/immunology ; Up-Regulation/immunology
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-alpha or IL-1beta, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-kappaB activation was assessed by NF-kappaB-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-alpha and IL-1beta significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-kappaB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-alpha or IL-1beta augmented NF-kappaB activation and IL-8 production in response to PGN or LTA. Both PGN- and LTA-induced NF-kappaB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-alpha or IL-1beta primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Paik, Yong Han(백용한)
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Lee, Dong Ki(이동기) ORCID logo https://orcid.org/0000-0002-0048-9112
Lee, Sang In(이상인)
Lee, Se Joon(이세준) ORCID logo https://orcid.org/0000-0002-2695-2670
Chon, Chae Yoon(전재윤)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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