Cholecystokinin octapeptide inhibits tumor necrosis factor-? transcription and nuclear factor-?B activity induced by lipopolysaccharide in rat pulmonary interstitial macrophages / 中国病理生理杂志

ABSTRACT

AIM: To elucidate the anti-inflammatory mechanism of cholecystokinin octapeptide (CCK-8). METHODS: The pulmonary interstitial macrophages (PIMs) from rats were stimulated with LPS (1 mg?L~(-1)) in the presence or absence of CCK-8 (10~(-8)-10~(-6) mol?L~(-1)) or/and CCK receptor antagonist proglumide (2 mg?L~(-1)). The expression of TNF-? mRNA was assayed by reverse transcription polymerase chain reaction (RT-PCR) at 3 h of the stimulation, and nuclear factor-?B (NF-?B) binding activity was analyzed by electrophoretic mobility shift assay (EMSA) at 1 h of stimulation. The I?B? protein level in the cytoplasma at 30 min of the stimulation was detected by Western blot. RESULTS: CCK-8, at concentrations from 10~(-8) mol?L~(-1) to 10~(-6) mol?L~(-1) obviously inhibited LPS-induced TNF-? mRNA expression and NF-?B binding activity in a dose-dependent manner. Stimulation with LPS resulted in a reduction of I?B? protein level in PIMs, which was elevated by CCK-8. The effects of CCK-8 on NF-?B activity and I?B protein level were attenuated by CCK receptor antagonist proglumide. CONCLUSION: CCK-8 inhibits LPS-induced TNF-? mRNA expression by regulating NF-?B activity in rat PIMs, which is mediated through CCK receptors and inhibition of I?B? degradation. This represents one of the anti-inflammatory mechanisms of CCK-8.