Effects Of Aspirin-Triggered Lipoxin On The Interleukin -6 Induced Inflammatory Response In Astrocytes

ObjectiveTo explore the mechanism aspirin-triggered lipoxin(ATL) protect astrocytes from interleukin-6(IL-6) induced inflammatory injury..Methods(1) To evaluate the time and dose effects of ATL on PGE₂, IL-6 induced primary rat astrocytes were treated with ATL at the concentration of 10^-8M,10^-7M respecetively. Culture supernatants were harvested at 4, 8, 12, 16 and 24 hours; PGE₂ were assessed by enzyme-linked immunosorbent assay (ELISA) analysis. (2)To evaluate the effects of ATL on COX-2 mRNA and protein. IL-6 induced primary rat astrocytes were treated with ATL at the concentration of 10^-7M. COX-2 mRNA were assessed by reverse transcription polymerase chain reaction (RT-PCR) analysis and COX-2 proteins were assessed by western-blot assay (WB) analysis. (3) To evaluate whether JAK2-STAT3 sinagling pathway participated in the ATL protecting astrocytes from IL-6 induced inflammatory injury, proteins of p-JAK2 and p-STAT3 were extracted and were assessed by western-blot analysis.(4) To evaluate the effect of ATL on SOCS3, IL-6 induced primary rat astrocytes were treated with ATL at the concentration of 10^-7M, and SOCS3 mRNA were assessed by reverse transcription polymerase chain, and SOCS3 protein extracted and were assessed by western-blot assay analysis. Results (1) Compared with the control group, IL-6 increased PGE₂ expression in culture supernatants of astrocytes with a dose- and time-dependent manner (p<0.05). However, pre-treated with ATL astrocytes can abolish IL-6 effects (p<0.05). (2) Compared with the control group, IL-6 increased the expression of COX2mRNA and proteins (p<0.05). Pre-treated with ATL can reversed aboved effects (p<0.05). (3) Compared with the control group, IL-6 increased the proteins of p-JAK2and p-STAT3 (p<0.05). Pre-treated with ATL can reversed aboved effects (p<0.05) (4) Compared with the control group, IL-6 did not have prominent effect on SOCS3 mRNA expression and protein. Pre-treated with ATL can increase SOCS3 mRNA expression and proteins (p<0.05) compared with IL-6 group.ConclusionsATL can suppress COX-2 and PGE₂ expression induced by IL-6 on astrocytes through increasing SOCS3 and suppressing JAK2-STAT3 signaling pathway.