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

Expression of transcription factors NF-κB and AP-1 in nasal polyposis

Clinical & Experimental Allergy, 2008

The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood. To determine the expression of transcription factors [(nuclear factor-kappaB) NF-kappaB and (activator protein) AP-1], cytokines [IL-1beta, TNF-alpha and (granulocytes and macrophage colony-stimulating factor) GM-CSF], growth factor (b-FGF), chemokine (eotaxin-2) and adhesion molecule (ICAM-1) in NP in comparison with nasal mucosa controls. Methods Cross-sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c-Fos, IL-1beta, TNF-alpha, ICAM-1, b-FGF, eotaxin-2 and GM-CSF were analysed through RQ-PCR, and p65 and c-Fos were also analysed through Western blotting. NF-kappaB expression was increased in patients with NP when compared with control mucosa (P<0.05), whereas AP-1 expression did not differ significantly between groups. Expressions of IL-1beta, eotaxin-2 and b-FGF were also increased in patients with NP compared with controls (P<0.05). The transcription factor NF-kappaB is more expressed in NP than in control mucosa. This is important in NP because NF-kappaB can induce the transcription of cytokines, chemokines and adhesion molecules, which play an important role in the inflammatory process. Moreover, transcription factors influence the response to corticosteroids, which are the basis of NP treatment. Transcription factor AP-1 does not seem to have a significant role in the pathological process.

Expression analysis of VEGFA, FGF2, TGFβ1, EGF and IGF1 in human nasal polyposis

A better understanding of the expression profile of a group of angiogenic markers in nasal polyps (NPs) would contribute considerably to the investigation of the formation of NPs. The aim of this study was to evaluate the combined mRNA expression of vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), transforming growth factor ß1 (TGFß1), epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF1) in NPs obtained from 21 patients undergoing nasal polypectomy. Nasal mucosae were obtained from the adjacent inferior turbinates (AIT) and middle turbinates (AMT) of the patients, as well as from 11 control subjects undergoing nasal corrective surgery. Analysis was performed using real-time RT-PCR. VEGFA, TGFß1 and IGF1 exhibited significant over-expression in the NPs compared to the control turbinates, EGF did not exhibit significant expression, and FGF2 presented constant overexpression in the NPs compared to both the adjacent and control turbinates. Since its mRNA levels were positively correlated with all the corresponding levels of the rest of the growth factors studied, TGFß1 seems to be a key cytokine in interactions between NP cells and the leading molecule of the epithelial differentiation and tissue remodelling present in the disease. Many correlations between the transcript levels of the other growth factors arose in the NP group as well, supporting a co-regulation of these genes in nasal polyposis. Our conclusions were that that VEGFA and TGFß1 participate significantly in the formation of NPs, whereas FGF2 and IGF1 are implicated in nasal polyposis to a lesser, but still significant, extent. EGF does not seem to be actively involved in the NP evolution process.

iNOS Expression in Oral and Gastrointestinal Tract Mucosa

Digestive Diseases and Sciences, 2008

It is known that the overproduction of nitric oxide (NO) by nitric oxide synthase (NOS) occurs during the progression of various inflammatory diseases in intestinal tract. NOS inhibitors or inducible nitric oxide synthase (iNOS) gene expression inhibitors should be considered as potential anti-inflammatory agents, as NO synthesized by iNOS is related to various pathophysiological processes including inflammation. In order to understand the relationship between iNOS and pathological reactions such as the inflammatory process and malign transformation clearly, the existence and amount of constitutive expression should be determined. It is crucial to comprehend the harmful and protective amounts of iNOS expressions in order to clarify the relationship between iNOS and pathological processes. Evidently, only after this inspection is it possible to utilize iNOS as a marker and treatment instrument during the diagnosis and treatment of malign transformation and the inflammatory process.

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

Oxidative Medicine and Cellular Longevity

Sinonasal polyps are very common benign lesions of the nasal mucosa. Most of nasal polyps (NP) are idiopathic, and the pathophysiology of this disease is still incompletely understood. Nitric oxide (NO) is a reactive molecule generated by nitric oxide synthase (NOS). NO has been identified as an important mediator in airway function and pathogenesis of several respiratory system diseases. Histological and genetical expression of iNOS was detected to evaluate the role of NO in the pathogenesis of allergic (ANP) and nonallergic nasal polyps (NANP). Forty patients with nasal polyps (20 allergic and 20 nonallergic) were identified by history, clinical examination, and investigation. NPs were obtained from the middle turbinate (MT) during concha bullosa surgery. Twenty normal MT nasal tissues were taken as the control from patients undergoing concha bullosa surgery, without any evidence of allergy or inflammation. A nasal polyp specimen from each patient was subjected for immune-histoche...