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Role of Inflammatory Mediators in Liver Cells: Regulation of Collagen and Apoptosis Induction

This study by Marta Varela Rey, PhD, explores the regulation of type I collagen mRNA levels in hepatic stellate cells by inflammatory mediators like TNF-α and TGF-β. It examines the apoptotic processes induced by substances such as “Ecstasy” in culture rat liver cells, alongside the implications of hepatocyte microvilli loss associated with hepatic injury. Understanding these mechanisms may enhance our knowledge of liver pathophysiology and potential therapeutic targets for liver diseases.

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Role of Inflammatory Mediators in Liver Cells: Regulation of Collagen and Apoptosis Induction

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  1. ROLE OF INFLAMATORY MEDIATORS IN LIVER CELLS MARTA VARELA REY, PhD.

  2. Regulation of type I collagen mRNA levels by TNF-a and TGF-b in hepatic stellate cells. • Induction of apoptotic process by “Ecstasy” in culture rat liver cells. ? Loss of hepatocyte microvilli Space of Disse Hepatocytes HEPATIC INJURY EC TNF-a TGF-b HSC EC col1a1 KC TGF-b TGF-b TNFa EMP HSC activated KC activated

  3. PC-PLC N-SMasa FAN DAG DAG TRAF2 TRADD TRADD A-SMasa CERAMIDE CERAMIDE FADD MEKK1 MEKK SEK 1 MEK 1 col1a1 ERK JNK p38 MAPK

  4. PLC-PC N-SMasa FAN DAG DAG TRAF2 TRADD TRADD A-SMasa CERAMIDE CERAMIDE FADD MEKK1 MEKK PD98059 SEK 1 MEK 1 col1a1 ERK JNK p38 MAPK L-JNK-I1 SB203580

  5. Regulation oftype I collagen mRNA levels by TNF-a in HSC TNF-a (minutes) 0 2 5 15 60 JNK-p TNF-a 0 15 20 30 40 p38 MAPK TNF-a - + - + - + p38 MAPK-p SB203580 - - + + - - col1a1 - - - - + + L-JNK-l1 *a mRNA col1a1 (fold) MEKK1 *b *a SEK 1 p38 MAPK JNK TNF-a A-SMasa CERAMIDE L-JNK-I1 SB203580 Varela Rey et al. FEBS lett. 2002

  6. Regulation oftype I collagen mRNA levels by TNF-a and TGF-b in HSC n.sa CERAMIDE n.sb SMasa-N ERK-p mRNA col1a1 TNF-a - + - + - - + + PD98059 MEKK TNF-a (min) 0 15 60 MEK 1 ERK TNF-a PD98059

  7. TNF-a p38 MAPK col1a1 TGF-b

  8. Regulation oftype I collagen mRNA levels by TNF-a and TGF-b in HSC p38MAPK col1a1 TNF-a TGF-b 18 S col1a1 *a Levels of mRNA col1a1 *b *a Control TGF-b SB SB+TGF-b TGF-b (min) 0 30 40 p38 MAPK-p

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