Transforming growth factor beta in hepatitis C virus infection: in vivo and in vitro findings.
BACKGROUND
Hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD) worldwide. The chronicity is a result of viral persistence and the ability of the virus to escape from the immune mechanisms of the host. Transforming growth factor (TGF)-beta is a cytokine thought to be responsible for viral persistence and liver fibrogenesis.


METHODS
The present study examined the levels of TGF-beta messenger (m)RNA by reverse transcription polymerase chain reaction (RT-PCR) in 35 liver biopsies and HCV-transfected HepG2 cells.


RESULTS
Transforming growth factor-beta mRNA was detected in nine liver biopsies from patients with chronic HCV infection, but was not detected in patients with non-HCV-related CLD or controls. On quantitation by semiquantitative PCR, TGF-beta mRNA levels ranged from 10-4.75 to 10-12.8 amol (10-7.46 +/- 3.771) in liver biopsies of HCV-related CLD. No significant difference in TGF-beta receptor levels was observed by RT-PCR in HCV- or non-HCV-related CLD by immunohistochemistry. To correlate these findings with in vitro experiments, levels of TGF-beta mRNA and its receptors were determined by RT-PCR in HepG2 cells transfected with HCV and hepatitis B virus (HBV) constructs, using mock-transfected cells as control. The TGF-beta protein levels were quantitated in these cell supernatants by enzyme immunoassay. The TGF-beta mRNA and protein levels were two logs and approximately 30 times higher in HCV-transfected HepG2 cells than in HBV- and mock-transfected cells, respectively. The TGF-beta receptors in HepG2 cells were also downregulated in HCV-transfected cells as compared with mock-transfected cells.


CONCLUSIONS
These observations suggest upregulation of TGF-beta in HCV infection and a probable role for TGF-beta in the pathogenesis of HCV-related CLD.
Ray
Sumar
S
Virology Section, Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
Broor
Sohan L
SL
Vaishnav
Yash
Y
Sarkar
Chitra
C
Girish
Rachakonda
R
Dar
Lalit
L
Seth
Pradeep
P
Broor
Shobha
S
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018197:Hepatoblastoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta