Table 4.

Bioactions of SPMs on epithelial repair and oxidative stress, demonstrated in non-CF models.

Epithelial repair/Oxidative stress
Conditions	SPMs	Models	Bioactions	References
In vitro studies
Corneal injury	LXA4	Rabbit corneal epithelial cells	Increases cell proliferation and migration	Kenchegowda et al., 2011
	RvE1	Human corneal epithelial cell line	Stimulates migration	Zhang et al., 2010
Acute lung injury	LXA4	Human bronchial epithelial 16HBE cell line	Protects airway epithelial through inhibition of LPS-induced ROS production. Preserves E-cadherin expression	Cheng et al., 2016
	RvD1	Human primary alveolar type II epithelial cell Human primary lung fibroblast	Enhances cell wound repair and proliferation, differentiation. Reduces apoptosis. Inhibits TGF-Beta-induced epithelial-mesenchymal transition. Inhibits fibroproliferation and myofibroblast differentiation of human lung fibroblasts	Zheng et al., 2018
TNF-α treatment	RvD1	Rat parotid Par-C10 cell line	Inhibits tight junction and cytoskeletal disruption Stimulates cell migration and polarity	Odusanwo et al., 2012
Cigarette smoke	RvD1, RvD2	Human primary peripheral blood monocytes and macrophages, and alveolar macrophages	Decrease levels of protein carbonylation after 24h	Croasdell et al., 2015
	RvD1	Human bronchial epithelial 16HBE cell line	Reduces the production of extracellular H2O2	Jiajia et al., 2014
	AT-RvD1	Male C57BL/6 mice (lung)	Reduces oxidative stress markers and ROS in BAL Restores elastic fibers Reduces alveolar enlargement	Posso et al., 2018
Microbial sepsis	RvD2 analog	Primary human PMNs; primary human umbilical vein endothelial cell (HUVEC)	Inhibits extracellular superoxide generation	Spite et al., 2009
Other	LXA4	Human bronchial epithelial 16HBE14o- cell line	Stimulates formation of tight junction through ZO-1, occludin, claudin-1 expression	Grumbach et al., 2009
	RvD1	Murine macrophages RAW264.7 cell line	Inactivates NADPH oxidase (NOX). Increases anti-apoptotic proteins	Lee and Surh, 2013
In vivo studies
Corneal injury	LXA4	C57BL/6 mice	Reduces surface area of injury	Kakazu et al., 2012
	RvD1	Diabetic C57BL/6 mice	Stimulates regeneration of the corneal epithelium Diminishes ROS accumulation by increasing GSH synthesis and decreasing NOX expression	Zhang et al., 2018
Acute lung injury	LXA4	BALB/c mice	Protects airway epithelial through inhibition of LPS-induced ROS production. Preserves E-cadherin expression	Cheng et al., 2016
	RvD1		Reduces production of lipid peroxidation malondialdehyde. Increases expression of SOD and HO-1 mRNA	Wang Q. et al., 2014