Tumor Necrosis Factor Alpha Modulates Transforming Growth Factor Alpha Espression Following Chemically-Induced Hepatoxicity

Details

• Personal Author:
  Gallucci RM ; Luster MI ; Simeonova PP ; Toriumi W
• Description:
  Previous studies have shown that Tumor Necrosis Factor-a (TNF-a) expression is increased in the livers of experimental animals following exposure to the hepatotoxin carbon tetrachloride (CCl4). In addition, administering neutralizing antibodies to TNF-a (anti- TNF-a) prior to exposure to CCI4 delays the regenerative process of the liver. We hypothesized that TNF-a may influence liver regenerative processes through modulation of liver derived growth factors. Mice were administered anti-TNF-a prior to CCI4 treatment. Antibody treatment did not affect the mRNA expression, as assessed by RT-PCR, of hepatocyte growth factor, its receptor c-met, epidermal growth factor, epidermal growth factor receptor (EGFR), or acidic fibroblast growth factor. Anti- TNF-a also did not affect liver EGFR number or binding. However, anti- TNF-a decreased the expression of transforming growth factor alpha (TGF-a) approximately 2.5 fold 12 and 24 hours post CC14, administration. To confirm this finding ribonuclease protection assays were performed and similar results to that shown with RT- PCR were found. lnterleukin-6 (IL6) has been shown to be necessary for liver regeneration following partial hepatectomy, and TNF-a can induce the expression of IL6 in liver. To assess whether TNF-a directly modulates TGF- a expression in the murine liver, recombinant murine TNF-a or recombinant murine IL6 was administered. TNF-a upregulated TGF-a expression approximately four fold above control levels, whereas IL6 did not affect TGF-a mRNA expression 90 minutes post injection. Taken together, these data indicate that TNF-a modulates the expression of TGF-a in the liver following hepatotoxic injury with CCI4, and that this modulation is independent of IL6 induction. [Description provided by NIOSH]
• Subjects:
  Animals Digestive System Digestive System Diseases Laboratories Liver Neoplasms Occupational Health Safety
• Keywords:
  Animal-studies Hepatotoxicity Hepatotoxins Laboratory-animals Liver-damage Liver-disorders Liver-function Liver-tissue Tumors
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  42
• NIOSHTIC Number:
  nn:20025101
• Citation:
  Toxicologist 1998 Mar; 42(1-S):272
• CAS Registry Number:
  Carbon tetrachloride (CAS RN 56-23-5)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:31bc19d25d803b8b574a234fef754b98d90a5f181a67c085f08fe3f652868a7752474b1cd59fe43df47f38aecf43766a2f49bece1844b567d40792a1aa85f97e
• Download URL:
  https://stacks.cdc.gov/view/cdc/196598/cdc_196598_DS1.pdf
• File Type:
  [PDF - 352.70 KB ]