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MARTA VARELA REY, PhD.

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

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MARTA VARELA REY, PhD.

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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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