Inhibitory effects of CCK-8 on NF-κB activities stimulated by LPS in rat PIMs

AIM: To investigate the inhibitory effects of cholecystokinin octapeptide (CCK-8) on nuclear factor-κB (NF-κB) activities stimulated by lipopolysaccharide (LPS) by using forskolin, the activator of adenylate cyclase, and PKA inhibitor H-89 in rat pulmonary interstitial macrophages (PIMs).METHODS: PIMs were isolated and purified.EMDA was applied to detect NF-κB activities and Western blotting was used to analyze the IκB-α protein level in rat PIMs.RESULTS: The NF-κB activity was not detected in normal control rat PIMs.The NF-κB activity in LPS-treated rat PIMs was obviously higher than that in control group (P<0.01).The IκB-α protein level in endochylema decreased obviously compared to control group (P<0.01).No obvious change of NF-κB activity and IκB-α protein level in CCK or Fsk treated rat PIMs was observed (P>0.05).The NF-κB activity in CCK＋LPS group and LPS＋Fsk group were obviously lower than that in LPS group (P<0.05).The IκB-α protein level was obviously higher (P<0.01).In LPS＋CCK＋H-89 group, the NF-κB activity in rat PIMs was obviously higher than that in CCK＋LPS group (P<0.01), while the IκB-α protein level decreased (P<0.01).CONCLUSIONS: The activation of cAMP-PKA signaling pathway inhibits the increase in NF-κB activity and the decrease in IκB-α protein level stimulated by LPS in rat PIMs.The anti-inflammatory effects of CCK-8 were taken effect by activating cAMP-PKA signaling pathway and further inhibiting the NF-κB activity.