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2015 ; 10
(11
): e0143141
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In Vivo Availability of Pro-Resolving Lipid Mediators in Oxazolone Induced Dermal
Inflammation in the Mouse
#MMPMID26599340
Homann J
; Suo J
; Schmidt M
; de Bruin N
; Scholich K
; Geisslinger G
; Ferreirós N
PLoS One
2015[]; 10
(11
): e0143141
PMID26599340
show ga
The activation and infiltration of polymorphonuclear neutrophils (PMN) are
critical key steps in inflammation. PMN-mediated inflammation is limited by
anti-inflammatory and pro-resolving mechanisms, including specialized
pro-resolving lipid mediators (SPM). We examined the effects of 15-epi-LXA4 on
inflammation and the biosynthesis of pro-inflammatory mediators, such as
prostaglandins, leukotriene B4 and various hydroxyeicosatetraenoic acids and SPM,
in an oxazolone (OXA)-induced hypersensitivity model for dermal inflammation.
15-epi-LXA4 (100 ?M, 5 ?L subcutaneously injected) significantly (P < 0.05)
reduced inflammation in skin, 24 hours after the OXA challenge, as compared to
skin treated with vehicle. No significant influence on the biosynthesis of
prostaglandins or leukotriene B4 was observed, whereas the level of
15S-hydroxy-eicosatetraenoic acid was significantly (P < 0.05) lower in the skin
areas treated with 15-epi-LXA4. In spite of the use of a fully validated
analytical procedure, no SPM were detected in the biological samples. To
investigate the reason for the lack of analytical signal, we tried to mimic the
production of SPM (lipoxins, resolvins, maresin and protectin) by injecting them
subcutaneously into the skin of mice and studying the in vivo availability and
distribution of the compounds. All analytes showed very little lateral
distribution in skin tissue and their levels were markedly decreased (> 95%) 2
hours after injection. However, docosahexaenoic acid derivatives were
biologically more stable than SPM derived from arachidonic acid or
eicosapentaenoic acid.
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