title: Altered NF-kappaB gene expression and collagen formation induced by polyunsaturated fatty acids.
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.
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907-2026, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: John J
authors.initials: JJ
authors.lastname: Turek
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000494:pharmacology; D041701:Swiss 3T3 Cells
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D016718:Arachidonic Acid; C002669:parthenolide; D003094:Collagen; D015118:Eicosapentaenoic Acid