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Epidermal growth factor and interleukin-1beta synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells.
Am J Physiol Gastrointest Liver Physiol. 2004 Dec; 287(6):G1188-93.AJ

Abstract

Epidermal growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1beta in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-kappaB (IkappaB), NF-kappaB, and Akt, were analyzed. IL-1beta stimulated the degradation of IkappaB and the activation of NF-kappaB but had no effect on iNOS induction. EGF, which had no effect on the NF-kappaB activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1beta stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1beta stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-kappaB through IkappaB kinase, respectively. Simultaneous addition of EGF and IL-1beta can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury.

Authors+Show Affiliations

Second Department of Surgery, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8506, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15271652

Citation

Kitagawa, Katsuhiko, et al. "Epidermal Growth Factor and Interleukin-1beta Synergistically Stimulate the Production of Nitric Oxide in Rat Intestinal Epithelial Cells." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 287, no. 6, 2004, pp. G1188-93.
Kitagawa K, Hamada Y, Kato Y, et al. Epidermal growth factor and interleukin-1beta synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2004;287(6):G1188-93.
Kitagawa, K., Hamada, Y., Kato, Y., Nakai, K., Nishizawa, M., Ito, S., & Okumura, T. (2004). Epidermal growth factor and interleukin-1beta synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells. American Journal of Physiology. Gastrointestinal and Liver Physiology, 287(6), G1188-93.
Kitagawa K, et al. Epidermal Growth Factor and Interleukin-1beta Synergistically Stimulate the Production of Nitric Oxide in Rat Intestinal Epithelial Cells. Am J Physiol Gastrointest Liver Physiol. 2004;287(6):G1188-93. PubMed PMID: 15271652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal growth factor and interleukin-1beta synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells. AU - Kitagawa,Katsuhiko, AU - Hamada,Yoshinori, AU - Kato,Yasunori, AU - Nakai,Koji, AU - Nishizawa,Mikio, AU - Ito,Seiji, AU - Okumura,Tadayoshi, Y1 - 2004/07/22/ PY - 2004/7/24/pubmed PY - 2004/12/21/medline PY - 2004/7/24/entrez SP - G1188 EP - 93 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 287 IS - 6 N2 - Epidermal growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1beta in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-kappaB (IkappaB), NF-kappaB, and Akt, were analyzed. IL-1beta stimulated the degradation of IkappaB and the activation of NF-kappaB but had no effect on iNOS induction. EGF, which had no effect on the NF-kappaB activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1beta stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1beta stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-kappaB through IkappaB kinase, respectively. Simultaneous addition of EGF and IL-1beta can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/15271652/Epidermal_growth_factor_and_interleukin_1beta_synergistically_stimulate_the_production_of_nitric_oxide_in_rat_intestinal_epithelial_cells_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00254.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -