NEW YORK (Reuters Health) - Expression of genes involved in the innate immune response is upregulated in nasal polyposis (NP) tissue, whereas a gene that inhibits the allergic immune response is sharply underexpressed, researchers report in the October issue of the Journal of Allergy and Clinical Immunology.
The product of this underexpressed gene, Clara cell 10-kd protein (CC10), is currently approved for treating lung disease in premature infants, and the investigators are now in preliminary talks with its manufacturer to develop trials of CC10 in NP, Dr. Bruce S. Bochner of Johns Hopkins told Reuters Health.
There is currently no effective treatment for NP, and the etiology of the disease is unknown. “This is truly a disease in search of some new ideas,” Dr. Bochner said.
Dr. Bochner and his colleagues used microarray analysis to compare gene expression in tissue from 10 NP patients and normal sphenoid sinus mucosa from four people without the condition. The aim was to find genes with at least a two-fold alteration in expression.
The researchers identified 192 upregulated genes and 156 downregulated genes. For validation, they tested mRNA and protein levels of the most altered genes in another set of tissue samples.
RT-PCR and immunohistochemistry confirmed elevated expression of prolactin-produced protein (PIP), lactoferrin and deleted in malignant brain tumor 1 (DMBT1) in the NP tissue, as well as lower CC10 expression.
The researchers note that lactoferrin and PIP both play a role in innate immune defense, and CC10 is thought to have both anti-inflammatory and immunomodulating effects. CC10 activity was 20-fold lower in the NP tissue, despite the fact that all of the NP patients were taking steroids and these drugs tend to increase CC10 levels.
DMBT1 appears to be involved in the growth and proliferation of epithelial cell structures, Dr. Bochner noted. “The fact that this one is way up, and the fact that nasal polyps themselves are these overgrowths of the lining of the sinus mucosa, makes me wonder whether for some reason there’s just overactive proliferation of these cells that then leads to polyp generation,” he concluded.
Source: J Allergy Clin Immunol 2004;114:783-790. [ Google search on this article ]
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