PT  - JOURNAL ARTICLE
AU  - Dezheng Zhao
AU  - Yanai Zhan
AU  - Huiyan Zeng
AU  - Hon-Wai Koon
AU  - Mary P. Moyer
AU  - Charalabos Pothoulakis
TI  - Neurotensin Stimulates Interleukin-8 Expression through Modulation of IκBα Phosphorylation and p65 Transcriptional Activity: Involvement of Protein Kinase Cα
AID  - 10.1124/mol.104.010801
DP  - 2005 Jun 01
TA  - Molecular Pharmacology
PG  - 2025--2031
VI  - 67
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/67/6/2025.short
4100  - http://molpharm.aspetjournals.org/content/67/6/2025.full
SO  - Mol Pharmacol2005 Jun 01; 67
AB  - Neurotensin (NT) is released in the gastrointestinal tract and participates in the pathophysiology of colonic inflammation. We have shown that NT mediates acute intestinal inflammation in vivo and stimulates nuclear factor-κB–dependent interleukin (IL)-8 expression in nontransformed human colonocytes in vitro. However, the exact mechanisms by which NT induces IL-8 expression have not been elucidated. In this study, we first show that NT stimulates IκBα phosphorylation and degradation and p65 phosphorylation and transcriptional activity. Inhibition of protein kinase C (PKC) activation significantly attenuates NT-induced IL-8 expression. This effect seems to be mediated through inhibition of IκBα phosphorylation and degradation and by p65 phosphorylation and transcriptional activity. We also show that intracellular calcium mobilization is necessary for NT-induced phosphorylation of IκBα and p65, suggesting that a conventional PKC is involved. Furthermore, transfection of a dominant-negative form of PKCα significantly reduces NT-induced IL-8 promoter activity. These results indicate that the conventional PKCα is an important mediator in the proinflammatory signaling pathway elicited by NT at the colonocyte level.