What is it about?
This work demonstrates that the IL1-beta autocrine loop, induced by a CFTR activity reduction, mediates the upregulation of epiregulin, resulting in the activation of the epidermal growth factor receptor (EGFR). Other lingands of EGFR are also upregulated.
Featured Image
Why is it important?
EGFR is involved in cell proliferation, tissue repair and cancer. Therefore, the CFTR activity and the IL-1b loop could have both important roles in the innate immune and inflammatory responses that have been associated with wound healing and cancer development. In addition, this work adds additional support to the previous findings regarding the role of chloride as a proinflammatory signal (Clauzure et al. Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells. J Cell Biochem. 2017;118(8):2131-2140. doi: 10.1002/jcb.25850.), which may have an important role in diseases in which the proinflammatory state could be a trigger through Cl- channels that reduce their expression, such as CFTR in cystic fibrosis, COPD, asthma, and cancer.
Perspectives
It was a great pleasure to do this work with Macarena, a former graduate student and now a posdoctoral student in my lab. Further work is now in progress to determine the physiological relevance of the EGFR activation in cells with impaired CFTR activity. The accumulation of Cl- is responsible for initiation of the IL-1b loop and the vicious negative feedback loop of IL-1b. This may have consequences in many diseases in which fibrosis and oxidative stress are involved through IL-1b, not only cystic fibrosis, including neurodegenerative diseases, heart fibrosis, etc. Further readings: 1: Massip-Copiz MM, Santa-Coloma TA. Extracellular pH and lung infections in cystic fibrosis. Eur J Cell Biol. 2018 Aug;97(6):402-410. doi: 10.1016/j.ejcb.2018.06.001. Epub 2018 Jun 18. Review. PubMed PMID: 29933921. 2: Valdivieso ÁG, Dugour AV, Sotomayor V, Clauzure M, Figueroa JM, Santa-Coloma TA. N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells. Redox Biol. 2018 Jun;16:294-302. doi: 10.1016/j.redox.2018.03.006. Epub 2018 Mar 14. PubMed PMID: 29573703; PubMed Central PMCID: PMC5953002. 3: Massip-Copiz M, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function. J Cell Biochem. 2018 Mar;119(3):2911-2922. doi: 10.1002/jcb.26483. Epub 2017 Nov 24. PubMed PMID: 29091309. 4: Valdivieso ÁG, Mori C, Clauzure M, Massip-Copiz M, Santa-Coloma TA. CFTR modulates RPS27 gene expression using chloride anion as signaling effector. Arch Biochem Biophys. 2017 Nov 1;633:103-109. doi: 10.1016/j.abb.2017.09.014. Epub 2017 Sep 21. PubMed PMID: 28941802. 5: Massip-Copiz MM, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling. Arch Biochem Biophys. 2017 Feb 15;616:1-12. doi: 10.1016/j.abb.2017.01.003. Epub 2017 Jan 11. PubMed PMID: 28088327. 6: Clauzure M, Valdivieso ÁG, Massip-Copiz MM, Mori C, Dugour AV, Figueroa JM, Santa-Coloma TA. Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells. J Cell Biochem. 2017 Aug;118(8):2131-2140. doi: 10.1002/jcb.25850. Epub 2017 Apr 18. PubMed PMID: 27996167. 7: Massip Copiz MM, Santa Coloma TA. c- Src and its role in cystic fibrosis. Eur J Cell Biol. 2016 Oct;95(10):401-413. doi: 10.1016/j.ejcb.2016.08.001. Epub 2016 Aug 11. Review. PubMed PMID: 27530912. 8: Valdivieso ÁG, Clauzure M, Massip-Copiz M, Santa-Coloma TA. The Chloride Anion Acts as a Second Messenger in Mammalian Cells - Modifying the Expression of Specific Genes. Cell Physiol Biochem. 2016;38(1):49-64. doi: 10.1159/000438608. Epub 2016 Jan 8. PubMed PMID: 26741366. 9: Clauzure M, Valdivieso AG, Massip Copiz MM, Schulman G, Teiber ML, Santa-Coloma TA. Disruption of interleukin-1β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function. PLoS One. 2014 Jun 5;9(6):e99257. doi: 10.1371/journal.pone.0099257. eCollection 2014. PubMed PMID: 24901709; PubMed Central PMCID: PMC4047112. 10: Valdivieso AG, Santa-Coloma TA. CFTR activity and mitochondrial function. Redox Biol. 2013 Feb 5;1:190-202. doi: 10.1016/j.redox.2012.11.007. Review. PubMed PMID: 24024153; PubMed Central PMCID: PMC3757715. 11: Valdivieso AG, Clauzure M, Marín MC, Taminelli GL, Massip Copiz MM, Sánchez F, Schulman G, Teiber ML, Santa-Coloma TA. The mitochondrial complex I activity is reduced in cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function. PLoS One. 2012;7(11):e48059. doi: 10.1371/journal.pone.0048059. Epub 2012 Nov 21. PubMed PMID: 23185247; PubMed Central PMCID: PMC3504030. 12: Valdivieso ÁG, Marín MC, Clauzure M, Santa-Coloma TA. Measurement of cystic fibrosis transmembrane conductance regulator activity using fluorescence spectrophotometry. Anal Biochem. 2011 Nov 15;418(2):231-7. doi: 10.1016/j.ab.2011.07.029. Epub 2011 Jul 30. PubMed PMID: 21864494. 13: Taminelli GL, Sotomayor V, Valdivieso AG, Teiber ML, Marín MC, Santa-Coloma TA. CISD1 codifies a mitochondrial protein upregulated by the CFTR channel. Biochem Biophys Res Commun. 2008 Jan 25;365(4):856-62. Epub 2007 Nov 29. PubMed PMID: 18047834. 14: Valdivieso AG, Marcucci F, Taminelli G, Guerrico AG, Alvarez S, Teiber ML, Dankert MA, Santa-Coloma TA. The expression of the mitochondrial gene MT-ND4 is downregulated in cystic fibrosis. Biochem Biophys Res Commun. 2007 May 11;356(3):805-9. Epub 2007 Mar 19. PubMed PMID: 17382898.
Dr Tomás A. Santa Coloma
Institute for Biomedical Research (BIOMED), CONICET, UCA
Read the Original
This page is a summary of: Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function, Journal of Cellular Biochemistry, November 2017, Wiley,
DOI: 10.1002/jcb.26483.
You can read the full text:
Contributors
The following have contributed to this page
