Author/Editor		Sodin-Šemrl, S; Spagnolo, A; Mikus, R; Barbaro, B; Varga, J; Fiore, S
Title		Opposing regulation of interleukin-8 and NF-kB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor
Type		članek
Source		Int J Immunopath Ph
Vol. and No.		Letnik 17, št. 2
Publication year		2004
Volume		str. 145-55
Language		eng
Abstract		Lipoxin A4 (LXA4) is a potent eicosanoid that inhibits IL-1beta-induced activation of human fibroblastlike synoviocytes (FLS) via the LXA4 receptor (ALXR). Serum amyloid A (SAA) is an acute phase reactant with cylokine-like properties. SAA has been shown to bind the same seven transmembrane G proteincoupled 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-kB 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 slably expressing ALXR in order to determine the role of NF-kB and/or AP-1 in the regulation of IL-8 gene expression. The NF-kB 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.
Descriptors		ARTHRITIS, RHEUMATOID AMYLOID FIBROBLASTS INTERLEUKIN-8 NF-KAPPA B CELLS, CULTURED DNA DOWN-REGULATION (PHYSIOLOGY) ELECTROPHORESIS ENZYME-LINKED IMMUNOSORBENT ASSAY METALLOPROTEINASES PROMOTER REGIONS (GENETICS) SYNOVIAL MEMBRANE TRANSFECTION STROMELYSIN 1