Altered NF-kappaB gene expression and collagen formation induced by polyunsaturated fatty acids

J Nutr Biochem. 2005 Aug;16(8):500-6. doi: 10.1016/j.jnutbio.2005.01.016.

Abstract

Inability to control collagen formation in vital organs (e.g., fibrosis) or stimulate healthy collagen production (CP) in connective tissues (e.g., ligaments) is a major cause of death and disability. This study tested the hypothesis that arachidonic acid (AA) and eicosapentaenoic acid (EPA) influenced CP in 3T3-Swiss fibroblasts by altering gene expression in the nuclear factor-kappa B (NF-kappaB) pathway. 3T3-Swiss fibroblasts were grown in medium containing either AA or EPA. Lipopolysaccharide (LPS) was used to activate NF-kappaB, and parthenolide was used to block it. Cells treated with EPA had increased expression of genes in the NF-kappaB pathway when exposed to LPS and also produced more collagen. Parthenolide blocked NF-kappaB activation to a greater extent in EPA-treated cells and also decreased CP induced by NF-kappaB activation. Genes in the NF-kappaB signaling pathway that had increased expression in EPA-treated cells included the toll-like receptor 4 (Tlr4), adaptor proteins [TNF receptor-associated factor 6 (Traf6), myeloid differentiation primary response gene 88], signal transduction kinases (NF-kappaB-inducing kinase, inhibitors of kappa light polypeptide gene enhancer isoforms), inhibitor protein (I-kappaB alpha chain), transcription factors (nuclear factor of kappa light chain gene enhancer, (p)105 and NF-kappaB subunit p100), DNA binding proteins (cAMP response element binding protein) and response genes known to affect CP [interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1]. This study raises the possibility that fatty acids may be used as adjuvants in combination with other therapies (e.g., selective targeting of the NF-kappaB pathway) to control collagen formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology*
  • Collagen / biosynthesis*
  • Eicosapentaenoic Acid / pharmacology*
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Lipopolysaccharides / pharmacology
  • Mice
  • NF-kappa B / biosynthesis*
  • Sesquiterpenes / pharmacology
  • Swiss 3T3 Cells

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Sesquiterpenes
  • Arachidonic Acid
  • parthenolide
  • Collagen
  • Eicosapentaenoic Acid