Am J Physiol Gastrointest Liver Physiol 286: G1032-G1041, 2004.
First published January 22, 2004; doi:10.1152/ajpgi.00473.2003
0193-1857/04 $5.00
INFLAMMATION/IMMUNITY/MEDIATORS
Inflammation of the cystic fibrosis mouse small intestine
Oxana Norkina,
Simran Kaur,
Donna Ziemer, and
Robert C. De Lisle
Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas 66160
Submitted 7 November 2003
; accepted in final form 20 January 2004
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 
2-glycoprotein (21-fold), resistin-like molecule-
(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.
innate defense; mast cell; neutrophil; Muclin; deleted in mammalian brain tumor 1
Address for reprint requests and other correspondence: R. C. De Lisle, Dept. of Anatomy and Cell Biology, Univ. of Kansas School of Medicine, Kansas City, KS 66160 (E-mail rdelisle{at}kumc.edu).
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Copyright © 2004 by the American Physiological Society.
