Gene interactions and pathways from curated databases and text-mining
Int J Immunopathol Pharmacol 2004, PMID: 15171815

Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor.

Sodin-Semrl, S; Spagnolo, A; Mikus, R; Barbaro, B; Varga, J; Fiore, S

Lipoxin A4 (LXA4) is a potent eicosanoid that inhibits IL-1beta-induced activation of human fibroblast like synoviocytes (FLS) via the ALX4 receptor. Serum amyloid A (SAA) is an acute phase reactant with cytokine-like properties. SAA has been shown to bind the same seven transmembrane G protein-coupled receptor ligated by LXA4. Here we compared the inflammatory responses of lipid (LXA4) and peptide (SAA) ligands in human FLS via the shared ALX, and characterized their downstream signaling. LXA4 induced stimulation of tissue inhibitors of metalloproteinase-2, whereas SAA induced interleukin-8 and matrix metalloproteinase-3 production. SAA up-regulated NF-kappaB and AP-1 DNA binding activity, while LXA4 markedly inhibited these responses after IL-1beta stimulation. A human IL-8 promoter luciferase construct was transfected into CHO cells stably expressing ALXR in order to determine the role of NF-kappaB and/or AP-1 in the regulation of IL-8 gene expression. The NF-kappaB pathway proved to be the preeminent for the biological responses elicited by both ligands. These findings suggest that two endogenous molecules, targeting a common receptor, could participate in the pathogenesis of inflammatory arthritis by differentially regulating inflammatory responses in tissues expressing the ALXR.

Diseases/Pathways annotated by Medline MESH: Arthritis, Rheumatoid
Document information provided by NCBI PubMed

Text Mining Data

interleukin-8 — serum amyloid A: " Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor "

NF-kappaB — serum amyloid A: " Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor "

AP-1 → SAA: " SAA up-regulated NF-kappaB and AP-1 DNA binding activity, while LXA4 markedly inhibited these responses after IL-1beta stimulation "

NF-kappaB → SAA: " SAA up-regulated NF-kappaB and AP-1 DNA binding activity, while LXA4 markedly inhibited these responses after IL-1beta stimulation "

IL-8 ⊣ AP-1: " A human IL-8 promoter luciferase construct was transfected into CHO cells stably expressing ALXR in order to determine the role of NF-kappaB and/or AP-1 in the regulation of IL-8 gene expression "

IL-8 ⊣ NF-kappaB: " A human IL-8 promoter luciferase construct was transfected into CHO cells stably expressing ALXR in order to determine the role of NF-kappaB and/or AP-1 in the regulation of IL-8 gene expression "

Manually curated Databases

No curated data.