Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis

Abstract

Nasal polyps (NP), edematous projections of nasal mucosa (NM), are characterized by an inflammatory cellular infiltrate, however, little is known about etiopathogenesis of NP. Both innate immune mechanisms leading to activation of NF-kappaB and homeostasis of epithelial cells were implicated in the pathogenesis of NP. In this study we investigated the expression of insulin-like growth factor-1 receptor (IGF-1R) and inducible nitric-oxide synthase (iNOS) in NP compared to healthy NM in both the epithelial and stromal compartments. Using immunohistochemistry, frozen tissue sections of NP from 18 patients, and mucosal biopsy specimens of the inferior turbinate from 17 subjects were stained for IGF-1R and iNOS markers. Fluorescence microscopy and computerized image analysis revealed low numbers of IGF-1R-positive cells in all specimens. However, substantially increased numbers of IGF-1R-positive cells were found in NP compared to NM both within the epithelium (1.63 vs. 0.43) and stroma (3.27 vs. 1.03). Positivity for iNOS was detected within the epithelium of NP compared with NM. Numbers of iNOS-positive single cells were highly increased in NP vs. NM in both epithelial (3.83 vs. 1.08) and stromal (4.96 vs. 2.67) compartments. An increased iNOS expression within the epithelial layer as well as increased number of iNOS- and IGF-1R-positive cells in NP was observed. This suggests that innate immune mechanism, and to a lesser extent also growth and homeostasis of epithelial cells, may play a role in formation of NP.

Overexpression of Inducible Nitric Oxide Synthase in Allergic and Nonallergic Nasal Polyp

“…The reduction of NOS2 (iNOS) expression in patients with chronic sinusitis and NP has been described [21, 22]. Our results agree with a previous study; it was found that the numbers of positive cells (epithelial and stromal) of both iNOS and insulin-like growth factor-1 receptor were highly increased in NP compared to normal mucosa [23].…”

Anti-proliferative activities of Centella asiatica extracts on human respiratory epithelial cells in vitro

“…Activated epithelial cells may be the major source of mediators inducing influx of inflammatory cells that further cause proliferation and activation of fibroblasts leading to nasal polyp formation (Pawliczak et al, 2005). The innate immune mechanism, the growth and homeostasis of epithelial cells may also play a role in the formation of nasal polyps (Fundova et al, 2008). Since the present study revealed that C. asiatica aqueous extract exhibited some inhibitory effect on the proliferation of human respiratory epithelial cells, the identification and characterization of the compounds present in C. asiatica extract to determine their particular functions will be part of our future study.…”

Effect of long-term, low-dose clarithromycin on T helper 2 cytokines, eosinophilic cationic protein and the ‘regulated on activation, normal T cell expressed and secreted’ chemokine in the nasal secretions of patients with nasal polyposis

“…Fundová and colleagues' results 19 suggest that nasal polyp pathogenesis and growth may be promoted by dysregulation of innate immune mechanisms (e.g. signalling via toll-like receptors and induction of nuclear factor κB and therefore cytokine production) and defective homeostasis of epithelial cells (with prolonged cell survival).…”