Inflammation of the cystic fibrosis mouse small intestine.
The CFTR null mouse [cystic fibrosis (CF) mouse] has a severe intestinal phenotype that serves as a model for CF-related growth deficiency, meconium ileus, and distal intestinal obstructive syndrome. DNA microarray analysis was used to investigate gene expression in the CF mouse small intestine. Sixty-one genes exhibited a statistically significant twofold or greater increase in expression, and 98 genes were downregulated twofold or greater. Of the upregulated genes, most were associated with inflammation and included markers for cells of the innate immune system (mast cells and neutrophils) and for acute-phase genes (serum amyloid A and complement factors). The downregulated genes include 10 cytochrome P-450 genes; several are involved in lipid metabolism, and several are involved in various transport processes. Confirmation by quantitative RT-PCR showed gene expression was significantly increased for mast cell protease 2 (27-fold), hematopoietic cell transcript 1 (17-fold), serum amyloid A3 (2.9-fold), suppressor of cytokine signaling 3 (2.0-fold), leucine-rich alpha(2)-glycoprotein (21-fold), resistin-like molecule-beta (49-fold), and Muclin (2.5-fold) and was significantly decreased for cytochrome P-450 4a10 (28-fold) and cubilin (114-fold). Immune cell infiltration was confirmed histologically by staining for mast cells and neutrophils. These data demonstrate that the CF intestine exhibits an inflammatory state with upregulation of components of the innate immune system.
Norkina
Oxana
O
Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Kaur
Simran
S
Ziemer
Donna
D
De Lisle
Robert C
RC
D000818:Animals; D002135:Calcium-Binding Proteins; D003199:Computer Systems; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency; D004268:DNA-Binding Proteins; D004751:Enteritis / Q000209:etiology* / Q000473:pathology; D020869:Gene Expression Profiling; D006729:Hormones, Ectopic / Q000378:metabolism; D007107:Immune System / Q000473:pathology; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D009077:Mucins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D052243:Resistin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C114202:Dmbt1 protein, mouse; D006729:Hormones, Ectopic; D009077:Mucins; D052243:Resistin; C499623:Retn protein, mouse; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D025521:Tumor Suppressor Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator