Transforming growth factor β (TGFβ) stimulates biosynthesis of matrix proteins in cultured liver sinusoidal endothelial cells from guinea pig

206 ACID SYNTHESIS ISOO:;If,i~~~T~~ IN CHRONIC BILE FREE ~1ICROSORAL OBSTRUCTION. BILIARY CHOLESTEROL REGULATE BILE ACID SYNTHESIS? Reichen. S. Duelan;e;;t R.A. Davis. Dept. Clin. J. Swtzerland and the Univ. Pharmacol.. Hepatobiliary Center, UCHSC: Denver, U.S.A. Bile acids (BA) are thought to be the aain regulators of 6A synthesis. In spite of Interrupting cholesterol (X0;) excretion by bile duct lipation XOL synthesis is maintained in biliary cirr(RDL). hosis (Hepatolosy 9:S37). To elucidate wechanism(s) of regulation of SA synthesrs. we eeasured serum BA. urinary BA excretion and microsoeal 7-a- hydroxylase activity, the ratelimiting enzysie of BA synthesis in control (CTR) and CDL rats. After four weeks of obstruction. serum EA (2+SDD YS 56+20 UK; pcO.001) and urinary BA secretion (0.0s $02 vs 19pxD.005) were markedly elevated. Vi+11 umoles/d: %xomal XOL was increased (ptD.005). !:ost aspects of wcrosomol function were decrease? in viva (ABT 29+2 YS E1+2: pcO.DDl) and in vitro (P450 0.45 ~0~09 vs 0;33+0.@9 nmoles/mg; ~0.?5). In marked 7adydroxylase (1823 vs 4125 +moles/nnnl contrast. kg.p
205

IN VIVD AND IN VITRO CdIDOGEN-LIVER GENE-EXPRESSION. STUDIES IN NORMAL AN0 IN CCL4DAMAGED RAT LIVER AND IN LIVER CELLS G. Ramadori, S. SchwGgler, Th. Veit, H. Rieder. K.H. Meyer zum Wschenfelde I. Department of Internal Medicine, University of Mainz, FRG Normal rat liver as well as CCL acutely and chronically

damaged

rat liv :! I-S were

analysed for nidogen gene expression by immunochemistry and by northern blotting of the total RNA extracted from the same gene expression was also livers. Nidogen studied in isolated rat hepatocytes, ITOKupffer cells and endothelial cells. cells,

In normal rat liver nidogen

staining

could

be detected in the vessel wall. A positive staining was found among the cells of the inflammatory infiltrates of acutely damaged liver and in the connective tissue septa of Nidogen specific transthe fibrotic liver. cripts were detectable in RNA from the acutely damaged liver and in even higher amounts in RNA from the chronically damaged liver. Synthesis and secretion of nidogen in ITD-cells but not in other hepatic cells could be demonstrated at protein as well as at RNA level. Protein and RNA transcripts from ITD-cells were similar to those found in arterial smooth muscle cells and skin fibroblasts. Conclusions: ITO-cells may be responsable for nidogen synthesis in liver fibrosis.

TRANSFORMING GROWfH FACTOR A (TGFS) STIMULATES SYNTHESIS OFMATR~XPROTEINSINCULTUREDLIVERSINUSOIDAL ENDOTHELIAL CEUS FROM G”lNEA PI0 KRioder. KlinikundPoliklinik.UniversityofMlinL FRO.

208 GMMA/DELl!A wm.k~mO~EuMl~S

BIO-

CEILS

IN

CRRCNIC

REPAlTRS

C OF

JI.Riezu.MP.Ci~.J.Canrw.A.CMtilla.J.~eto. xp,t.of Medicine.univ.of Navaml.psaplma. spa .

1. Medidoi9cbs

Most T cells posseasAlfa/l&a T cell receptor and -58 CD~m01ecules.bsmall 8ubpopulation of CD3 ,Alfa/l!eta-,GmmalDcIta+ been recently described.lbis

lpnphocptes

has

sobset exhibits poteot cytolitic activity and is believed to be involved in the eliraination of infactad or otlmwise stressad cells.Using FACS malywx and two colout fkxeacence we have determinedthe nunbar of cD3+.Gml6alDe1ta+ lgmphocgt+ain 24 controls and 114 blood samplesfran CR ptients (anti-HCV+)dividad into the folloaing groqm:33 patients dtbout prior treatmalt (group 1).47 al IlW for OS-3 mooths(group2).23 oo IFNfor 6-12 monthsCgcup 3) aod 11 1-5 moothaafter caqletioo IIN treahnnt kpalp 4).In mmbzrof Gmm/Delta+ T cells mfi61 2 :3$ cells/@

rwpectively)

was

similar

to calwols

(85t37LIn contraat.~s 3 and 4 ahwad a ;tcFant elevation of this T cell uubsst (1 22112 and 134*UJ8;pCO.05 and pCO.01respecCmclusions: l.IFti induces a positive modulation of

wun&e1ta+

T

cells

only

after

pro1cngc.d

admioistratioo. 2.‘Ihis finding might be relavant to axplaio the mad for long-term IFN therapyto achieve

S52

control

of CHC.