Cl- acts as a second messenger and pro-inflammatory signal

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These results increase our knowledge regarding the CFTR signaling and the effects of Cl- on gene expression, acting as a second messenger for CFTR or other Cl- channels or transporters. Since IL-1b initiates a cascade of pro-inflammatory processes, these effects of Cl- on its secretion and expression suggest that Cl- is a pro-inflammatory effector. Interestingly, the excessive common salt (NaCl) intake might be not only dangerous because of the hypertensive Na+ effects but also due to the pro-inflammatory effects of Cl-. References: 1: 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. 2: 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. 3: 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. 4: 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. 5: 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. 6: 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. 7: 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. 8: 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. 9: 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. 10: 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. 11: González-Guerrico AM, Cafferata EG, Radrizzani M, Marcucci F, Gruenert D, Pivetta OH, Favaloro RR, Laguens R, Perrone SV, Gallo GC, Santa-Coloma TA. Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis. J Biol Chem. 2002 May 10;277(19):17239-47. Epub 2002 Feb 28. PubMed PMID: 11872746. 12: Cafferata EG, Guerrico AM, Pivetta OH, Santa-Coloma TA. NF-kappaB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1beta. J Biol Chem. 2001 May 4;276(18):15441-4. Epub 2001Feb 5. PubMed PMID: 11278608. 13: Cafferata EG, González-Guerrico AM, Giordano L, Pivetta OH, Santa-Coloma TA. Interleukin-1beta regulates CFTR expression in human intestinal T84 cells. Biochim Biophys Acta. 2000 Feb 21;1500(2):241-8. PubMed PMID: 10657593. 14: Cafferata EG, Gonzalez-Guerrico AM, Pivetta OH, Santa-Coloma TA. Identification by differential display of a mRNA specifically induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in T84 human colon carcinoma cells. Cell Mol Biol (Noisy-le-grand). 1996 Jul;42(5):797-804. PubMed PMID: 8832110.

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