Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein

Pierluigi Baron, Gabriela Constantin, Annalisa D'Andrea, Diego Ponzin, Elio Scarpini, Guglielmo Scarlato, Giorgio Trinchieri, Filippo Rossi, Marco A. Cassatella

Research output: Contribution to journalArticle

Abstract

In this study we examined the effect of myelin P2 protein on some proinflammatory functions exerted by human mononuclear phagocytes. Northern blot analysis demonstrated that P2 protein selectively induced in monocytes and macrophages mRNA accumulation of tumor necrosis factor (TNF), interleukin 1β (IL-1β), and interleukin 8 (IL-8) in a time-dependent manner. Natural killer stimulating factor (IL-12) mRNA and protein secretion was strongly induced by lipopolysaccharide but not by P2 protein. Supernatants harvested from P2-stimulated monocytes contained significant amounts of TNF, IL-1β, and IL-8, whereas those from macrophages contained only TNF and IL-8. The effect of the P2 protein on TNF and IL-8 mRNA accumulation and secretion was not affected by polymyxin B, which, on the other hand, almost completely abolished the effect of lipopolysaccharide. Finally, P2 protein did not directly trigger hydrogen peroxide release but, through the induced release of TNF, potentiated monocyte respiratory burst capability. Since P2 protein is the antigen responsible for the induction of experimental allergic neuritis, these findings identify a potential mechanism involved in the inflammatory reaction and myelin damage during experimental allergic neuritis.

Original languageEnglish
Pages (from-to)4414-4418
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number10
Publication statusPublished - May 15 1993

Keywords

  • Experimental allergic neuritis
  • Interleukin 1
  • Interleukin 12
  • Interleukin 8

ASJC Scopus subject areas

  • General
  • Genetics

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