Down-regulation of the Anti-inflammatory Protein Annexin A1 in Cystic Fibrosis Knock-out Mice and Patients

• DOI: 10.1074/mcp.m500019-mcp200
• Publication Date: 2005-07-13T12:10:23Z
• Authors: Noura Bensalem; Ana Paula Ventura; Benoît Vallée; Joanna Lipecka; Danielle Tondelier; Noélie Davezac; Alexandre Dos Santos; Mauro Perretti; Anne Fajac; Isabelle Sermet-G...; Michel Renouil; Jean-François Lesure; Frédéric Halgand; Olivier Laprévote; Aleksander Edelman
• Keywords: Annexin A1; Annexin A2; Proinflammatory cytokine; Annexin A5

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