Nuclear factor-κB activation in human monocytes stimulated with lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous PGE₂

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• 作者：Conte ; Enrico ; Bonaiuto ; Corrada ; Nesci ; Caterina ; Crimi ; Nunzio ; Vancheri ; Carlo ; Messina ; Angelo
• 关键词：Nuclear factor κ ; B ; Monocyte ; Macrophage ; Lipopolysaccharide ; Fibroblast ; Prostaglandin E₂
• 刊名：FEBS Letters
• 出版年：1997
• 出版时间：January 6, 1997
• 年：1997
• 卷：400
• 期：3
• 页码：315-318
• 全文大小：490 K

文摘

The nuclear factor κB (NF-κB) is thought to be crucially involved in the gene activation of several cytokines, including tumor necrosis factor α (TNF). Previously, we showed that fibroblast conditioned medium (FCM) is able to inhibit both TNF mRNA accumulation and protein release in peripheral blood-derived human monocytes (PBM) stimulated with lipopolysaccharide (LPS). In this study we have investigated the effect of FCM on the LPS-induced DNA-binding activity of NF-κB, by means of electrophoretic shift assay (EMSA). We provide evidence that FCM strongly inhibits the LPS-induced NFκB activation in PBM. Furthermore, we show that exogenous PGE₂ mimics the NFκB inhibitory effect of FCM. On the other hand, FCM produced in the presence of indomethacin does not inhibit NF-κB activation by LPS. Our results lend further support to the hypothesis that inflammatory and immune responses of monocytes/macrophages may be modulated at the molecular level by signals originating from tissue structural cells such as fibroblasts.