Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin

Licheng Tian, Julie E. White, Hung Yun Lin, Visa S. Haran, Joseph Sacco, G. Chikkappa, Faith B. Davis, Paul J. Davis, Min Fu Tsan

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Endotoxin selectively induces monocyte Mn superoxide dismutase (SOD) without affecting levels of Cu,Zn SOD, catalase, or glutathione peroxidase. However, little is known about the structure-activity relationship and the mechanism by which endotoxin induces Mn SOD. In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E. coli endotoxin and markedly stimulated the activation of human monocyte nuclear factor-κB and the induction of Mn SOD mRNA and enzyme activity. However, in contrast to the wild-type endotoxin, it failed to induce significant production of tumor necrosis factor-α and macrophage inflammatory protein-1α by monocytes and did not induce the phosphorylation and nuclear translocation of mitogenactivated protein kinase. These results suggest that 1) lipid A myristoyl fatty acid, although it is important for the induction of inflammatory cytokine production by human monocytes, is not necessary for the induction of Mn SOD, 2) endotoxin-mediated induction of Mn SOD and inflammatory cytokines are regulated, at least in part, through different signal transduction pathways, and 3) failure of the mutant endotoxin to induce tumor necrosis factor-α production is, at least in part, due to its inability to activate mitogen-activated protein kinase.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number3 44-3
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Endotoxins
Superoxide Dismutase
Monocytes
Cytokines
Lipid A
Fatty Acids
Tumor Necrosis Factor-alpha
Macrophage Inflammatory Proteins
Horseshoe Crabs
Signal transduction
Phosphorylation
Enzyme activity
Structure-Activity Relationship
Glutathione Peroxidase
Mitogen-Activated Protein Kinases
Catalase
Protein Kinases
Signal Transduction
Chemical activation
Messenger RNA

Keywords

  • Lipopolysaccharide
  • Mitogen- activated protein kinase
  • Nuclear factor-κB
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin. / Tian, Licheng; White, Julie E.; Lin, Hung Yun; Haran, Visa S.; Sacco, Joseph; Chikkappa, G.; Davis, Faith B.; Davis, Paul J.; Tsan, Min Fu.

In: American Journal of Physiology - Cell Physiology, Vol. 275, No. 3 44-3, 1998.

Research output: Contribution to journalArticle

Tian, L, White, JE, Lin, HY, Haran, VS, Sacco, J, Chikkappa, G, Davis, FB, Davis, PJ & Tsan, MF 1998, 'Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin', American Journal of Physiology - Cell Physiology, vol. 275, no. 3 44-3.
Tian, Licheng ; White, Julie E. ; Lin, Hung Yun ; Haran, Visa S. ; Sacco, Joseph ; Chikkappa, G. ; Davis, Faith B. ; Davis, Paul J. ; Tsan, Min Fu. / Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin. In: American Journal of Physiology - Cell Physiology. 1998 ; Vol. 275, No. 3 44-3.
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