Expression of genes that encode the annexin-1 and galectin-1 proteins in nasal polyposis and their modulation by glucocorticoid

Braz J Otorhinolaryngol. 2010;76(2):213-8. ORIGINAL ARTICLE Expression of genes that encode the annexin-1 and galectin-1 proteins in nasal polyposis and their modulation by glucocorticoid Atílio Maximino Fernandes 1, Erica Babeto 2, Paula Rahal 3, Paola Jocelan Scarin Provazzi 4, Claudia Augusta Hidalgo 5, Wilma T. Anselmo-Lima 6 Keywords: annexin a1, galectin 1, glucocorticoids, nasal polyps. Summary R hinosinusal polyps physiopathology is not fully understand, despite numerous hypotheses regarding its inflammatory process. Aims: a prospective study regarding the gene expression of proteins: anexin-1 and galectin-1, which has an anti-inflammatory action and is modulated by steroids. Materials and Methods: eleven patients with rhinosinusal polyps suffered a biopsy of their polyps at two moments: in the absence of systemic steroids and during its use. In the two samples we assessed the expression of these genes and compared it to the normal nasal mucosa in the middle meatus. Results: We noticed that the mean expression of the genes which code anexin-1 and galectin-1 was predominantly increased, regardless of the use of steroids in relation to the control nasal mucosa. Notwithstanding, in polyps without the use of steroids, the mean gene expression of anexin-1 was significantly higher than in the polyps which were under the use of steroids. Regarding galectin-1, there was no significant difference between the expression mean values before and after the use of systemic steroids. Conclusion: The genes present an expression increase in the polyp mucosa, regardless of the use of steroids; nonetheless, the relationship of these two genes of anti-inflammatory proteins with steroids did not happen the same way. Doctorate, physician of the otorhinolaryngology and head & neck surgery department of Famerp, São José do Rio Preto, SP. 2 Master’s degree in genetics, doctoral student in the biology department, Ibilce/UNESP, São José do Rio Preto. 3 Doctorate, adjunct professor of the biology department, Ibilce/UNESP, São José do Rio Preto. 4 Master’s degree, doctoral student in the biology department, Ibilce/UNESP, São José do Rio Preto. 5 Doctorate, adjunct professor of mathematics, UNIP, São José do Rio Preto. 6 Associate professor of the ophthalmology, otorhinolaryngology and head & neck surgery department, Ribeirão Preto Medical School, USP. Paper submitted to the BJORL-SGP (Publishing Management System – Brazilian Journal of Otorhinolaryngology) on May 30, 2009; and accepted on July 24, 2009. cod. 6420 1 Brazilian Journal of Otorhinolaryngology 76 (2) March/April 2010 http://www.bjorl.org / e-mail: 213 INTRODUCTION tolerance. Its exact in vivo function remains uncertain because of rupture of the galectin-1 gene; however, studies with galectin-1 inhibitors in rats have shown inhibition of acute inflammation, probably by a decreased inflow of polymorphonuclear cells.8 Immunohistochemical studies involving comparisons between the nasal mucosa of the lower and middle nasal turbinates and nasal polyps and between allergic and non-allergic subjects have shown variable galectin expression in the nasal mucosa. Galectin-1 is expressed more in polyps compared to the middle and lower turbinates; however, a higher expression of galectin-1 has been found in the lower nasal turbinate compared to the middle turbinate. Allergic patients also express more galectin-1, although this difference appears not to be significant.9 Such variability raises questions about the possible involvement of galectin-1 in inflammation in nasal polyps. Some authors have questioned whether increased expression of galectin-1 in the lower turbinate, compared to the middle turbinate, would be an anti-inflammatory protective effect with subsequent inhibition of polyp growth; this could explain the absence of polypoid degeneration in the lower turbinate. Increased expression in polyps may be an uncontrolled attempt to block pre-installed inflammation. We therefore decided to investigate the expression of genes that code these two anti-inflammatory proteins (annexin-1 and galectin-1) in nasal polyps and their response when systemic glucocorticoids are given. Nasal polyps may be characterized by edema of the nasal mucosa associated with degeneration of variable intensity. It generally begins on the middle meatus bilaterally, and may extend to the paranasal sinuses and nasal fossae, probably associated with various clinical etiopathogenic entities.1 Recently, nasal polyps as a condition was classified in the chronic rhinosinusitis subgroup, where the common symptoms are nasal congestion and nasal block, facial pain, anterior or posterior discharge, and decreased olfaction; nasal polyps, however, may be differentiated by the presence of bilateral polypoid degeneration in the nasal meatuses.2 Lack of a clear definition is due to poor understanding of the etiopathogeny of this condition. It is clear that tissue inflammation with eosinophilia is the main feature of inflammatory and edematous polyps, which comprise about 90% of nasal polyps. However, the mediators of inflammation in this situation are not a conventional inflammatory process; eosinophilic inflammation becomes persistent and unrelated to known mechanisms of atopy. A multifactor cause has been suggested, in which there is a resulting variable degeneration of the nasal mucosa, which results in nasal block, loss of olfaction, and recurring rhinosinusitis.3 Animal models have shown that anti-inflammatory proteins, such as annexin-1 and galectin-1, are involved in inflammation. They appear to mediate inflammation when glucocorticoids are administered.4-6 Annexin-1 is a family of 12 protein found in mammals; these proteins are able to bind to phospholipids and calcium. They are frequent in mammal tissues, with a discreet distribution in certain epithelial cells, such as those of the respiratory and urinary systems, the skin, the synovial, macrophages and tissue leukocytes.7 Annexin-1 has been implied in several intracellular processes, such as intracellular signal transduction, cytoskeleton membrane binding, proliferation and differentiation. Its antiinflammatory function is attributed to its ability to inhibit phospholipase A2 and to bind to specific granulocyte and macrophage surface receptors, inhibiting leukocyte diapedesis.7 It has also been demonstrated that glucocorticoids may induce annexin-1 synthesis in monocytes and neutrophils, but not in other cell lineages; in these, glucocorticoid-induced annexin-1 expression is related with cell growth and differentiation. Galectins are a specific family of lecithins that bind to galactosides. Galectin-1 was the first to be described; it consists of a homodimeric protein, expressed mainly in lymphoid organs such as the thymus, lymph nodes, activated macrophages and T cells. This suggests an important relation with the generation and maintenance immune PATIENTS AND METHODS Nasal polyp specimens were tak (...truncated)