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- Title
Interactions Between Lipoxin A<sub>4</sub>, the Stable Analogue 16-phenoxy-lipoxin A<sub>4</sub> and Leukotriene B<sub>4</sub> in Cytokine Generation by Human Monocytes.
- Authors
Andersson, P.; Serhan, C. N.; Petasis, N. A.; Palmblad, J.
- Abstract
Lipoxins display both stimulatory and inhibitory actions with leucocytes that are cell-type dependent. We tested whether lipoxin A4 (LXA4) and its stable synthetic analogue 16-phenoxy-17-18,19,20-tetranor-lipoxin-A4 (16-phe-LXA4) modulated the ability of human blood monocytes (MO) to express mRNA and proteins for interleukin-1β (IL-1β), IL-6 and IL-1 receptor antagonist (IL-1Ra) in vitro and compared their actions with lipopolysaccharide (LPS) and leukotriene B4 (LTB4). 16-phe-LXA4, LPS and LTB4, but not LXA4, induced gene expression of IL-1β in MO. IL-1β protein synthesis increased by LPS (1500-fold), LTB4 (280-fold) and 16-phe-LXA4 (30-fold). Although the IL-1Ra gene was constitutively activated, mRNA concentration not affected by any of the stimulants, IL-Ra protein synthesis was increased by LPS (with 74%), 16-phe-LXA4 (35%) and LTB4 (20%), but not by LXA4. Each of these stimuli upregulated the IL-6 gene. Increases of IL-6 protein were 3000-fold for LPS, threefold for 16-phe-LXA4, eightfold for LXA4 and twofold for LTB4. Prior exposure of MO to 16-phe-LXA4, but not LXA4, reduced LTB4 induced synthesis of IL-1β with 66%, IL-6 with 20% and IL-1Ra with 29%. Thus, a stable LXA analogue, that resists rapid inactivation by monocytes, displays novel actions in cytokine generation, intimately involved in the regulation of inflammation.
- Subjects
LEUCOCYTES; LIPOXINS; ARACHIDONIC acid; MONOCYTES; CYTOKINES; INTERLEUKIN-1
- Publication
Scandinavian Journal of Immunology, 2004, Vol 60, Issue 3, p249
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.0300-9475.2004.01469.x