Activated lymphocytes increase expression of 5-lipoxygenase and its activating protein in THP-1 cells

Abstract

The aim of this study was to investigate the regulation of the 5-lipoxygenase pathway of arachidonic acid metabolism by lymphocytes using the monocyte-like cell line, THP-1. When THP-1 cells were incubated over 4–7 days in 10% supernatant from lectin-activated human lymphocytes, their capacity to synthesize 5-lipoxygenase products was significantly increased. In contrast, the supernatant from nonactivated lymphocytes had no effect. The increase in capacity to synthesize 5-lipoxygenase products was mimicked by the addition of either granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin-3. These increases in synthetic capacity reflected increased enzymatic activity. Increased immunoreactive protein and mRNA for the enzymes 5-lipoxygenase and 5-lipoxygenase-activating protein were also found in cells conditioned with activated lymphocyte supernatants. Furthermore, the increase in mRNA for both enzymes was not blocked by cycloheximide, suggesting that the effect on steady-state mRNA levels does not require the synthesis of new protein. The increase in mRNA could be reproduced by GM-CSF. We conclude that lymphocytes can regulate the expression of 5-lipoxygenase in THP-1 cells over a period of days via the release of soluble factors.

The Molecular Biology and Regulation of 5-Lipoxygenase

“…The effect of the lymphocyte conditioned medium could be mimicked by GM-CSF or interleukin 3 (IL-3) (81). Similar results were obtained with the monocyte-like cell line THP-1 (82), and the same group also found that dexamethasone could increase expression of 5LO and FLAP in these cells (83). IL-3 can stimulate expression of 5LO also in mouse mast cells (84).…”

International Union of Pharmacology XLIV. Nomenclature for the Oxoeicosanoid Receptor

“…There is a marked increase in the quantities of 5-oxo-ETE only when neutrophils are pretreated with phorbol myristate acetate (PMA), which elevates NADP ϩ (Powell et al, 1994). Zhang and coworkers (1996) end products identified (Ring et al, 1996(Ring et al, , 1997Werz and Steinhilber, 1996;Bonizzi et al, 1997;Larsson et al, 1998;Werz et al, 2000). In the murine-elicited peritoneal macrophage, 5-oxo-ETE was also detected (Hevko et al, 2001;Heveko and Murphy, 2002).…”

Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases

“…GM-CSF stimulates the recruitment and activation of eosinophils via ␤ integrin-mediated adhesion to epithelial and endothelial cells (16) and prolongs eosinophil survival via inhibition of apoptosis (5,17,18). Moreover, GM-CSF stimulates activation of the 5-lipoxygenase pathway (19). In addition, murine models of asthma and dieselinduced hyper-responsiveness have demonstrated an association between epithelial cell-derived GM-CSF and airway hyper-responsiveness (20,21).…”