Volume 30, Issue 1, 2021
DOI: 10.24205/03276716.2020.2030
LxA4 Inhibits LPS Induced Proinflammatory Response and Microglia Polarization through Notch Signaling Pathway
Abstract
Objective: to analyze the inhibitory effect of lipoxin A4 (LXA4) on lipopolysaccharide (LPS)
- induced proinflammatory response and microglial polarization through Notch signaling
pathway.
Methods: mouse microglial BV2 cells were cultured in vitro and divided into control group
(serum-free medium), LXA4 group (100nmol /L LXA4), LPS induced group (200ng/ml LPS),
LXA4 + LPS group (100nmol / L LXA4 + 200ng / ml LPS), DAPT + LPS group (100nmol/L
LXA4+200ng/ml LPS), DAPT + LXA4 + LPS group (10μM DAPT+200ng/ml LPS). RT-PCR,
Western blot and ELISA were used to detect the effects of LxA4 on LPS induced
inflammatory response, polarization and downstream molecular activity of Notch
signaling pathway.
Results: the expression of IL-1 β and TNF - α mRNA in LXA4 + LPS group was significantly
lower than that in LPS induced group, while IL-10 mRNA expression was significantly
higher than that in LPS induced group (P < 0.05). The expression of iNOS mRNA and
protein in LXA4 + LPS group was significantly lower than that in LPS induced group, and
Argl mRNA and protein expression was higher than that in LPS induced group (P < 0.05).
Notch1, Hes1 mRNA and protein expressions in LXA4 + LPS group were significantly lower
than those in LPS induced group, and the expression of Hes5mRNA and protein in LXA4 +
LPS group was significantly higher than that in LPS induced group (P < 0.05). Compared
with DAPT + LPS group and LXA4 + LPS group, iNOSmRNA in DAPT+LXA4+LPS group was
significantly increased, and ArglmRNA was significantly decreased (P < 0.05). Compared
with DAPT + LPS group and LXA4 + LPS group, the levels of IL-1 β and TNF - α in
DAPT+LXA4+LPS group were significantly increased and IL-10 was decreased obviously (P
< 0.05).
Conclusion: LxA4 can inhibit LPS induced proinflammatory response and cell polarization
of microglia, and its mechanism may be related to the regulation of Notch signaling
pathway.
Keywords
LXA4; Notch signaling pathway; LPS; Microglia; Proinflammatory response; Polarization