Hepatocyte growth factor and keratinocyte growth factor enhance IL-1-induced IL-8 secretion through different mechanisms in Caco-2 epithelial cells

• Published in: In vitro cellular & developmental biology. Animal Vol. 47; no. 2; pp. 173 - 181
• Main Authors: Unger, Benjamin L, McGee, Dennis W
• Format: Journal Article
• Language: English
• Published: New York New York : Springer-Verlag 01.02.2011; Springer Science + Business Media; Springer-Verlag; Society for In Vitro Biology
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Androstadienes - pharmacology; Animal Genetics and Genomics; Biomedical and Life Sciences; Caco 2 cells; Cell Biology; Cell Culture; Cell growth; Cell migration; Cell Movement; Cultured cells; Cytokines; CYTOKINES/GROWTH FACTORS/ADHESION FACTORS; Developmental Biology; Epithelial cells; Fibroblast Growth Factor 7 - pharmacology; Fibroblast Growth Factor 7 - physiology; Hepatocyte growth factor; Hepatocyte Growth Factor - pharmacology; Hepatocyte Growth Factor - physiology; Hepatocytes; Humans; Inflammation; Inflammatory bowel diseases; Interleukin 1; Interleukin 8; Interleukin-1 - pharmacology; Interleukin-8 - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestine; Keratinocyte growth factor; Keratinocytes; Life Sciences; Mucosa; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - physiology; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - physiology; Secretion; Signal transduction; Signal Transduction - genetics; Stem Cells; Wortmannin; Wound healing; Wound Healing - physiology; PI3K; IL-1; Intestine; HGF; AKT; Inflammation; Colon; KGF; IL-8
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-010-9365-4

A variety of cytokines have been detected in inflamed intestinal mucosal tissues, including the pro-inflammatory cytokine, interleukin-1 (IL-1), along with growth factors involved in wound healing processes such as proliferation and cell migration. However, little is known about how IL-1 and growth factors interact with intestinal epithelial cells to regulate the production of inflammatory cytokines such as interleukin-8 (IL-8). Previously, we have shown that hepatocyte growth factor (HGF) could significantly enhance IL-1-stimulated IL-8 secretion by the Caco-2 colonic epithelial cell line, yet HGF, by itself, did not stimulate IL-8 secretion. In this report, a second growth factor, keratinocyte growth factor (KGF), was also found to significantly enhance IL-1-induced IL-8 secretion by Caco-2 cells, yet KGF, by itself, also had no effect. Simultaneous addition of both IL-1 and KGF was also required for the enhancing effect. Treatment of the Caco-2 cells with wortmannin or triciribine suppressed the enhancing effect of HGF, suggesting that the effect was mediated by signaling through phosphatidylinositol-3-kinase (PI3K) and the kinase AKT. The enhancing effect of KGF was not affected by wortmannin, but was suppressed by triciribine, suggesting that the effect of KGF was through a PI3K-independent activation of AKT. These results suggest that the growth factors HGF and KGF may play a role in enhancing IL-1-stimulated production of IL-8 by epithelial cells during mucosal inflammations. However, the mechanism by which the growth factors enhance the IL-1 response may be through different initial signaling pathways.