The role of Lipoxin A4 in endometrial biology and endometriosis

Abstract

Lipoxin A4 (LXA4), an endogenous anti-inflammatory and immunomodulatory mediator studied in many disease states, is recently appreciated as a potentially significant player in the endometrium. This eicosanoid, synthesized from arachidonic acid via the action of lipoxygenase enzymes, is likely regulated in endometrial tissue during the menstrual cycle. Recent studies revealed that LXA4 acts as an estrogen receptor agonist in endometrial epithelial cells, antagonizing some estrogen-mediated activities in a manner similar to the weak estrogen estriol, with which it shares structural similarity. LXA4 may also be an anti-inflammatory molecule in the endometrium, though its precise function in various physiological and pathological scenarios remains to be determined. The expression patterns for LXA4 and its receptor in the female reproductive tract suggest a role in pregnancy. The present review provides an oversight of its known and putative roles in the context of immuno-endocrine crosstalk. Endometriosis, a common inflammatory condition and a major cause of infertility and pain, is currently treated by surgery or anti-hormone therapies that are contraceptive and associated with undesirable side effects. LXA4 may represent a potential therapeutic and further research to elucidate its function in endometrial tissue and the peritoneal cavity will undoubtedly provide valuable insights.

Lipoxin A4 suppresses the development of endometriosis in an ALX receptor‐dependent manner via the p38 MAPK pathway

“…LXA 4 and its receptor ALX receptor involved regulating inflammatory events in the human endometrium and decidua of early pregnancy (Macdonald et al ., ). The ectopic endometrial tissues from women with EM showed an elevated expression of LXA 4 receptor compared with the normal tissues (Motohashi et al ., ; Canny and Lessey, ). The present finding also demonstrated a significant increase of ALX receptor gene and protein expression in ectopic endometrial tissues compared with the control endometrium.…”

The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution

“…In patients and in rat endometrium with ectopic endometriosis, ALX/FPR2 showed higher expression [127]. Since SPM like LXA 4 counter-regulate pro-inflammatory cytokines (Box I), LXA 4 reverses LPS-induced miscarriages down regulating both uterine and pro-inflammatory mediators from placenta and mast cells in this tissue [123], and may be useful in endometriosis-related infertility [128]. During stress, the mechanism involves inactivation of glucocorticoids inhibiting LX-biosynthesis [123] controlling local inflammatory-homeostasis in pregnancy, suggesting a physiologic role for SPM (Fig.…”

Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells

“…These resolution-phase mediators alter the magnitude and the duration of the inflammatory response through mechanisms involving counter regulation of inflammatory mediators as well as phagocytosis of microbes and cell debris18. Recent evidence suggests that LXs and Rvs also play a role under normal, physiological conditions1920212223. In conjunctival goblet cells, RvD1 and its epimer aspirin-triggered RvD1 (AT-RvD1), and RvE1 appear to have two functions (1) alone these compounds increase [Ca 2+ ] i , activate extracellular regulated kinase (ERK) 1/2, and stimulate mucin secretion and (2) block LTD 4 - and histamine-stimulated increase in [Ca 2+ ] i and mucin secretion1920.…”