Inhibition of LPS-Induced TNF-X Expression by Phenolic Antioxidants

Details

• Personal Author:
  Kinneer DeFede K ; Luster M ; Ma Q ; Ye J
• Description:
  Phenolic antioxidants exhibit anti-inflammatory, anti-atherosclerotic, and anti-carcinogenic activities in animals. The broad range of biological effects of the phenolic antioxidants suggests multiple mechanisms exist for their action. Tumor necrosis factor alpha (TNF-alpha) is an important regulator of immune and inflammatory responses and tumor growth, thus, is involved in may biological, as well as pathological processes. Bacterial endotoxin LPS stimulates production of TNF-alpha, a process essential to LPS-elicited inflammation and sepsis. Previous studies suggest that certain phenolic antioxidants protect against LPS toxicity. However, the mechanism of such protection is not known. In this report, we examine the effect of phenolic antioxidents on LPS-induced expression of TNF-alpha in macrophage cells. We found that tert-butylhydroquinone (tBHQ), a prototype of phenolic antioxidants, totally inhibity LPS-induced production of TNF-alpha protein. To further investigate the molecular mechanism of this inhibition, we generated a stable reporter cell line that expresses luciferase under the control of a TNF-alpha promoter region. Our results show that LPS induces luciferase production and tBHQ totally blocks this induction in the cell. This inhibition is both time- and dose-dependent. Furthermore, diphenols such as para-hydroquinone, catechol, and resorcinol also inhibit LPS-induced luciferase expression. The inhibition correlates with the redox potential of these chemicals, which implicates redox cycling as a mechanism for the inhibition of TNF-alpha. Our current goal is to identify the molecular target and pathway for the regulation of TNF-alpha production by phenolic antioxidants. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Carcinogens Neoplasms Occupational Health Safety
• Keywords:
  Animal Studies Biological Effects Phenolic Compounds Tumors
• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  180-181
• Volume:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20021353
• Citation:
  Toxicologist 2001 Mar; 60(1):180-181
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c80fd7744f40f321f97cc803a882167981014364c358172a20c639621a3337b412ce34d6df684a879eabce60c714a1375e5241af8d5770bec3fa45613ab3f185
• Download URL:
  https://stacks.cdc.gov/view/cdc/198711/cdc_198711_DS1.pdf
• File Type:
  [PDF - 141.51 KB ]