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Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients.
Mol Cell Proteomics 2005; 4(10):1591-601MC

Abstract

Cystic fibrosis is a fatal human genetic disease caused by mutations in the CFTR gene encoding a cAMP-activated chloride channel. It is characterized by abnormal fluid transport across secretory epithelia and chronic inflammation in lung, pancreas, and intestine. Because cystic fibrosis (CF) pathophysiology cannot be explained solely by dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR), we applied a proteomic approach (bidimensional electrophoresis and mass spectrometry) to search for differentially expressed proteins between mice lacking cftr (cftr(tm1Unc), cftr-/-) and controls using colonic crypts from young animals, i.e. prior to the development of intestinal inflammation. By analyzing total proteins separated in the range of pH 6-11, we detected 24 differentially expressed proteins (>2-fold). In this work, we focused on one of these proteins that was absent in two-dimensional gels from cftr-/- mice. This protein spot (molecular mass, 37 kDa; pI 7) was identified by mass spectrometry as annexin A1, an anti-inflammatory protein. Interestingly, annexin A1 was also undetectable in lungs and pancreas of cftr-/- mice, tissues known to express CFTR. Absence of this inhibitory mediator of the host inflammatory response was associated with colonic up-regulation of the proinflammatory cytosolic phospholipase A2. More importantly, annexin A1 was down-regulated in nasal epithelial cells from CF patients bearing homozygous nonsense mutations in the CFTR gene (Y122X, 489delC) and differentially expressed in F508del patients. These results suggest that annexin A1 may be a key protein involved in CF pathogenesis especially in relation to the not well defined field of inflammation in CF. We suggest that decreased expression of annexin A1 contributes to the worsening of the CF phenotype.

Authors+Show Affiliations

INSERM U467, Faculté de médecine Necker, Université Paris-Descartes, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

16014420

Citation

Bensalem, Noura, et al. "Down-regulation of the Anti-inflammatory Protein Annexin A1 in Cystic Fibrosis Knock-out Mice and Patients." Molecular & Cellular Proteomics : MCP, vol. 4, no. 10, 2005, pp. 1591-601.
Bensalem N, Ventura AP, Vallée B, et al. Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients. Mol Cell Proteomics. 2005;4(10):1591-601.
Bensalem, N., Ventura, A. P., Vallée, B., Lipecka, J., Tondelier, D., Davezac, N., ... Edelman, A. (2005). Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients. Molecular & Cellular Proteomics : MCP, 4(10), pp. 1591-601.
Bensalem N, et al. Down-regulation of the Anti-inflammatory Protein Annexin A1 in Cystic Fibrosis Knock-out Mice and Patients. Mol Cell Proteomics. 2005;4(10):1591-601. PubMed PMID: 16014420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients. AU - Bensalem,Noura, AU - Ventura,Ana Paula, AU - Vallée,Benoît, AU - Lipecka,Joanna, AU - Tondelier,Danielle, AU - Davezac,Noélie, AU - Dos Santos,Alexandre, AU - Perretti,Mauro, AU - Fajac,Anne, AU - Sermet-Gaudelus,Isabelle, AU - Renouil,Michel, AU - Lesure,Jean-François, AU - Halgand,Frédéric, AU - Laprévote,Olivier, AU - Edelman,Aleksander, Y1 - 2005/07/12/ PY - 2005/7/15/pubmed PY - 2006/2/24/medline PY - 2005/7/15/entrez SP - 1591 EP - 601 JF - Molecular & cellular proteomics : MCP JO - Mol. Cell Proteomics VL - 4 IS - 10 N2 - Cystic fibrosis is a fatal human genetic disease caused by mutations in the CFTR gene encoding a cAMP-activated chloride channel. It is characterized by abnormal fluid transport across secretory epithelia and chronic inflammation in lung, pancreas, and intestine. Because cystic fibrosis (CF) pathophysiology cannot be explained solely by dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR), we applied a proteomic approach (bidimensional electrophoresis and mass spectrometry) to search for differentially expressed proteins between mice lacking cftr (cftr(tm1Unc), cftr-/-) and controls using colonic crypts from young animals, i.e. prior to the development of intestinal inflammation. By analyzing total proteins separated in the range of pH 6-11, we detected 24 differentially expressed proteins (>2-fold). In this work, we focused on one of these proteins that was absent in two-dimensional gels from cftr-/- mice. This protein spot (molecular mass, 37 kDa; pI 7) was identified by mass spectrometry as annexin A1, an anti-inflammatory protein. Interestingly, annexin A1 was also undetectable in lungs and pancreas of cftr-/- mice, tissues known to express CFTR. Absence of this inhibitory mediator of the host inflammatory response was associated with colonic up-regulation of the proinflammatory cytosolic phospholipase A2. More importantly, annexin A1 was down-regulated in nasal epithelial cells from CF patients bearing homozygous nonsense mutations in the CFTR gene (Y122X, 489delC) and differentially expressed in F508del patients. These results suggest that annexin A1 may be a key protein involved in CF pathogenesis especially in relation to the not well defined field of inflammation in CF. We suggest that decreased expression of annexin A1 contributes to the worsening of the CF phenotype. SN - 1535-9476 UR - https://www.unboundmedicine.com/medline/citation/16014420/Down_regulation_of_the_anti_inflammatory_protein_annexin_A1_in_cystic_fibrosis_knock_out_mice_and_patients_ L2 - http://www.mcponline.org/cgi/pmidlookup?view=long&pmid=16014420 DB - PRIME DP - Unbound Medicine ER -