scholarly journals Induction of Monocyte Chemotactic Protein 1 in Colonic Epithelial Cells by Entamoeba histolytica Is Mediated via the Phosphatidylinositol 3-Kinase/p65 Pathway

2007 ◽  
Vol 75 (4) ◽  
pp. 1765-1770 ◽  
Author(s):  
Srinivas J. Kammanadiminti ◽  
Indranil Dey ◽  
Kris Chadee
Keyword(s):  
Epithelial Cells ◽  
Entamoeba Histolytica ◽  
Pi3 Kinase ◽  
Classical Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Colonic Epithelial Cells ◽  
Monocyte Chemotactic Protein ◽  
Mrna Induction ◽  
Chemotactic Protein ◽  
Phosphatidylinositol 3

ABSTRACT The role intestinal epithelial cells play in the pathogenesis of amebic colitis is poorly understood. Herein, we demonstrate that secreted and soluble ameba (Entamoeba histolytica) proteins (SAP) induce expression of the chemoattractant monocyte chemotactic protein (MCP) in the colonic epithelial cell lines Caco-2, T84, and LS174T. MCP-1 mRNA induction was both dose and time dependent, with peak induction occurring at 8 h and with 100 μg/ml of SAP. Significant increase in MCP-1 protein expression was observed after 12 h. SAP failed to activate any of the mitogen-activated protein kinase pathways or IκB kinase activity. Moreover, inhibiting the classical pathway of NF-κB activation did not affect SAP-induced MCP-1 expression. Instead, we find that SAP-induced MCP-1 expression is dependent on posttranslational modification of the NFκB p65 subunit. SAP induced phosphorylation of p65 and enhanced NF-κB transcriptional activity, which are phosphatidylinositol 3-kinase (PI3 kinase) dependent. Treatment with PI3 kinase inhibitor LY290004 significantly abrogated the activation of Akt, p65, and MCP-1 mRNA induction. We conclude that colonic epithelial cells play a role in the initiation of inflammation by secreting chemokines in response to soluble ameba components.

scholarly journals Regulatory role of phosphatidylinositol 3-kinase on TNF-α–Induced cyclooxygenase 2 expression in colonic epithelial cells

2001 ◽  
Vol 120 (5) ◽  
pp. 1117-1127 ◽  
Author(s):  
Sean A. Weaver ◽  
Maria Pia Russo ◽  
Karen L. Wright ◽  
George Kolios ◽  
Christian Jobin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Regulatory Role ◽  
Phosphatidylinositol 3 Kinase ◽  
Colonic Epithelial Cells ◽  
Tnf Α ◽  
Phosphatidylinositol 3

scholarly journals Regulation of Hepatic Insulin-Like Growth Factor-Binding Protein-1 Gene Expression by Insulin: Central Role for Mammalian Target of Rapamycin Independent of Forkhead Box O Proteins

Endocrinology ◽  
2006 ◽  
Vol 147 (5) ◽  
pp. 2383-2391 ◽  
Author(s):  
Catherine Mounier ◽  
Victor Dumas ◽  
Barry I. Posner
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
Binding Protein ◽  
Mammalian Target Of Rapamycin ◽  
Pi3 Kinase ◽  
Target Of Rapamycin ◽  
Mrna Levels ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Inhibition ◽  
Phosphatidylinositol 3

The expression of IGF-binding protein-1 (IGFBP-1) is induced in rat liver by dexamethasone and glucagon and is completely inhibited by 100 nm insulin. Various studies have implicated phosphatidylinositol 3-kinase, protein kinase B (Akt), phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1 (Foxo1)/Foxo3, and the mammalian target of rapamycin (mTOR) in insulin’s effect. In this study we examined insulin regulation of IGFBP-1 in both subconfluent and confluent hepatocytes. In subconfluent hepatocytes, insulin inhibition of IGFBP-1 mRNA levels was blocked by inhibiting PI3 kinase activation, and there was a corresponding inhibition of Foxo1/Foxo3 phosphorylation. In these same cells, inhibition of the insulin effect by rapamycin occurred in the presence of insulin-induced Foxo1/Foxo3 phosphorylation. In confluent hepatocytes, insulin could not activate the phosphatidylinositol 3-kinase (PI3 kinase)-Akt-Foxo1/Foxo3 pathway, but still inhibited IGFBP-1 gene expression in an mTOR-dependent manner. In subconfluent hepatocytes, the serine/threonine phosphatase inhibitor okadaic acid (100 nm) partially inhibited IGFBP-1 gene expression by 40%, but did not produce phosphorylation of either Akt or Foxo proteins. In contrast, 1 nm insulin inhibited the IGFBP-1 mRNA level by 40% and correspondingly activated Akt and Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nm insulin. These results suggest a potential role for a serine/threonine phosphatase(s) in the regulation of IGFBP-1 gene transcription, which is not downstream of mTOR and is independent of Akt. In conclusion, we have found that in rat liver, insulin inhibition of IGFBP-1 mRNA levels can occur in the absence of the phosphorylation of Foxo1/Foxo3, whereas activation of the mTOR pathway is both necessary and sufficient.

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