[HTML][HTML] Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing

AR Brogliato, AN Moor, SL Kesl, RF Guilherme… - Journal of Investigative …, 2014 - Elsevier
AR Brogliato, AN Moor, SL Kesl, RF Guilherme, JL Georgii, M Peters-Golden, C Canetti
Journal of Investigative Dermatology, 2014Elsevier
Lipid mediators derived from 5-lipoxygenase (5-LO) metabolism can activate both pro-and
anti-inflammatory pathways, but their role in wound healing remains largely unexplored. In
this study we show that 5-LO knockout (5-LO-/-) mice exhibited faster wound healing than
wild-type (WT) animals, and exhibited upregulation of heme oxygenase-1 (HO-1).
Furthermore, HO-1 inhibition in 5-LO-/-mice abolished the beneficial effect observed.
Despite the fact that 5-LO-/-mice exhibited faster healing, in in vitro assays both migration …
Lipid mediators derived from 5-lipoxygenase (5-LO) metabolism can activate both pro- and anti-inflammatory pathways, but their role in wound healing remains largely unexplored. In this study we show that 5-LO knockout (5-LO-/-) mice exhibited faster wound healing than wild-type (WT) animals, and exhibited upregulation of heme oxygenase-1 (HO-1). Furthermore, HO-1 inhibition in 5-LO-/- mice abolished the beneficial effect observed. Despite the fact that 5-LO-/- mice exhibited faster healing, in in vitro assays both migration and proliferation of human dermal fibroblasts (HDFs) were inhibited by the 5-LO pharmacologic inhibitor AA861. No changes were observed in the expression of fibronectin, transforming growth factor (I and III), and α-smooth muscle actin (α-SMA). Interestingly, AA861 treatment significantly decreased ROS formation by stimulated fibroblasts. Similar to 5-LO-/- mice, induction of HO-1, but not superoxide dismutase-2 (SOD-2), was also observed in response to 5-LO (AA861) or 5-LO activating protein (MK886) inhibitors. HO-1 induction was independent of nuclear factor (erythroid derived-2) like2 (Nrf-2), cyclooxygenase 2 (COX-2) products, or lipoxin action. Taken together, our results show that 5-LO disruption improves wound healing and alters fibroblast function by an antioxidant mechanism based on HO-1 induction. Overexpression of HO-1 in wounds may facilitate early wound resolution.
Elsevier