Effects of fatty acid nitroalkanes on signal transduction pathways and airway macrophage activation

Abstract

Fatty acid nitroalkenes are reversibly-reactive electrophiles that are endogenously detectable at nM concentrations and display anti-inflammatory, pro-survival actions. These actions are elicited through the alteration of signal transduction proteins via a Michael addition on nucleophilic cysteine thiols. Nitrated fatty acids (NO2-FAs), like 9- or 10-nitro-octadec-9-enolic acid, will act on signal transduction proteins directly or on key regulatory proteins to cause an up-regulation or down-regulation of the protein’s expression, yielding an anti-inflammatory response. These responses have been characterized in many organ systems, such as the cardiovascular system, with the pulmonary system less well defined. Macrophages are one of the most abundant immune cells in the lung and are essential in maintaining lung homeostasis. Despite this, macrophages can play a role in both acute and chronic lung injury due to up-regulation of anti-inflammatory signal transduction pathways and down-regulation of pro-inflammatory pathways. Through their propensity to alter signal transduction pathways, NO2-FAs may be able to reduce macrophage activation during pulmonary injury. This review will focus on the implications of NO2-FAs on macrophage activation in the lung and the signal transduction pathways that may be altered, leading to reduced pulmonary injury.

Analytical Toolbox to Unlock the Diversity of Oxidized Lipids

“…Some molecular species of nFAs were detected in vivo and shown to be elevated under inflammatory conditions . However, in contrast to oxidized FAs, known predominantly as pro-inflammatory mediators, nFAs are believed to play mostly an anti-inflammatory role and thus might serve as potential therapeutic agents . Here, to address the potential diversity of nFAs, we performed in vitro nitration of the four most abundant PUFAs, oleic acid (OA), linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA), using nitronium tetrafluoroborate acting as a donor of nitronium ions (NO 2 + ) under low oxygen tension (Figure A).…”