transforming-growth-factor-alpha and Nasal-Polyps

To evaluate the possible role of tight junction protein Occludin in nasal polyps.. The expression of Claudin-1, Occludin and ZO-1 in nasal polyps (n = 20) and healthy uncinate mucosa (n = 15) were examined using immunohistochemical staining, real-time quantitative polymerase chain reaction (PCR) and Western blot analysis. The regulatory effects of proinflammatory cytokines (IFN-γ, IL-13, IL-17, TGF-β, TGF-α) on the expression of Occludin in cultured human nasal epithelial cells were investigated.. The immunohistochemical results showed that Claudin-1, Occludin and ZO-1 were detected both in the nasal polyp group and the control group. The expression sites were the cell membrane and cytoplasm of nasal mucosa epithelial cells. The mean optical density of Claudin-1, Occludin and ZO-1 were 0.187 ± 0.076,0.172 ± 0.109 and 0.098 ± 0.035 respectively in the nasal polyp group and were significantly lower than those in the control group (0.312 ± 0.101, 0.220 ± 0.069 and 0.233 ± 0.093 respectively), the differences were significant (t = 9.345, t = 3.301, t = 13.323, all P < 0.01).RT-PCR results showed that the relative expression of Occludin mRNA was 0.000 117 ± 0.000 035 in the nasal polyp group and was significantly lower than that in the control group(0.000 464 ± 0.000 134), and the difference was significant (Z = -5.0, P < 0.01) . There was no statistically significant difference in the relative expression of Claudin-1 and ZO-1 mRNA between the nasal polyp group and the control group (P > 0.05) . After the cultured human nasal epithelial cells were stimulated by IL-13, IL-17, IFN-γ and other proinflammatory cytokines, the relative expression of Occludin mRNA was 0.631 ± 0.039, 0.581 ± 0.029 and 0.648 ± 0.040, respectively. Compared with the unstimulated control group, the differences were statistically significant (t = 16.299, 24.669 and 14.995 respectively, all P < 0.05).Western blot analyse showed that the relative grayscale in the above proinflammatory cytokines stimulation groups was 0.650 ± 0.061,0.482 ± 0.106 and 0.536 ± 0.109, respectively. Compared with the unstimulated control group, the differences were statistically significant (t = 9.880, 8.442 and 7.310 respectively, all P < 0.05).. The reduced expression of Occludin might be involved in the pathogenesis of nasal polyps.

Topics: Claudin-1; Cytokines; Epithelial Cells; Humans; Interleukin-13; Interleukin-17; Nasal Mucosa; Nasal Polyps; Occludin; RNA, Messenger; Tight Junctions; Transforming Growth Factor alpha; Zonula Occludens-1 Protein

To study the expression of transforming growth factor alpha, beta 1 in hyperplastic tissue after endoscopic polypectomy and the effect of corticosteroid.. Forty patients with nasal polyps were divided into two groups randomly: corticosteroid group (n = 20) with topical application of Budesonide (BUD, 400 micrograms/d) after endoscopic polypectomy and control group (n = 20) without corticosteroid after surgery. The hyperplastic tissues in operative cavity obtained in the 1st and 8th weeks after operation were studied with HE staining and immunohistochemistry technique respectively.. Morphological changes of hyperplastic tissue after endoscopic polypectomy included pseudostratified epithelium, highly edematous lamina proper and inflammatory cells infiltration, in which the main infiltrative cells were eosinophils (67.5%). Transforming growth factor alpha(TGF alpha) protein was highly expressed in epithelial cells, grand cells and inflammatory cells in the hyperplastic tissue. Transforming growth factor beta 1 (TGF beta 1) protein was highly expressed in inflammatory cells in the hyperplastic tissue. The expression of TGF alpha and beta 1 was significantly decreased after topical BUD spray (P < 0.01, 0.05).. Transforming growth factor alpha and beta 1 may play an important role in the formation and recurrence of nasal polyps.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Female; Humans; Hyperplasia; Male; Nasal Mucosa; Nasal Polyps; Transforming Growth Factor alpha; Transforming Growth Factor beta

To assess the possible role of expression of TGF alpha and EGFR in nasal polyps and its relationship with PCNA labeling index.. Specimens from 20 patients of nasal polyps were studied with immunohistochemical technique.. The expression of TGF alpha, EGFR and PCNA were increased in the epithelium, gland cells and inflammatory cells of nasal polyps. There was a close correlation between the intensities of TGF alpha, EGFR and PCNA.. TGF alpha may play a key role in epithelial cell proliferation in nasal polyps.

Topics: Adult; ErbB Receptors; Female; Humans; Male; Middle Aged; Nasal Polyps; Proliferating Cell Nuclear Antigen; Transforming Growth Factor alpha

Transforming growth factor-alpha (TGF-alpha) has been implicated in diverse physiologic and pathophysiologic functions including immunological, inflammatory, and neoplastic processes. TGF-alpha has been localized in the hyperproliferative, inflammatory environment of chronic otitis media, cholesteatoma, and asthmatic airways. TGF-beta1, which must be present with TGF-alpha to transform fibroblasts, has been found in rhinitic mucosa and in asthma in prior studies. The authors sought to identify whether TGF-alpha also played a role in the inflammatory cascade and fibrosis of rhinitis.. A nonrandomized, prospective study was carried out in which samples of inferior turbinate and nasal polyps from rhinitic and nonrhinitic patients were subjected to immunohistochemistry and Western blotting to determine the presence of TGF-alpha.. Twenty-seven subjects undergoing surgery for rhinitis, obstructive sleep apnea, nasal fracture, and rhinoplasty were recruited for this study, the latter three groups acting as controls. Immunohistochemical and Western blotting techniques were employed to identify the presence of TGF-alpha in inferior-turbinate and nasal-polyp samples of rhinitic subjects.. Immunohistochemistry demonstrated the selective staining of TGF-alpha in the basement membrane and extracellular matrix, including lymphatic, vascular, and glandular structures, in most turbinate samples and the absence of staining in corresponding controls. Further, TGF-alpha was isolated to a discrete 30-kD band in both inferior turbinate and polyp tissues by Western blotting without staining in the corresponding controls.. These results suggest that TGF-alpha may play a role in the inflammatory derangement of rhinitis.

Topics: Adolescent; Adult; Basement Membrane; Blotting, Western; Extracellular Matrix; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Polyps; Rhinitis; Transforming Growth Factor alpha; Turbinates

Nasal polyps are thought to develop as a manifestation of a chronic inflammatory process involving the upper airways. The eosinophil characteristically represents a prominent component of the inflammatory cell infiltrate of these lesions. However, the major clinical problem associated with nasal polyps, nasal obstruction, reflects the proliferation of the stromal and epithelial elements, which constitute the bulk of these lesions. We recently reported that blood eosinophils of patients with hypereosinophilia can produce the cytokines transforming growth factors-alpha (TGF-alpha) and beta 1 (TGF-beta 1). These cytokines have many biologic activities, which include the regulation of epithelial proliferation, the promotion of extracellular matrix formation, and the induction of angiogenesis. We therefore used in situ hybridization to determine whether the eosinophils that infiltrate nasal polyps express TGF-alpha and/or TGF-beta 1 messenger RNA and used immunohistochemistry to determine whether these eosinophils also express TGF-alpha and TGF-beta 1 proteins. We found that eosinophils represented a major source of both transforming growth factors in each case of nasal polyposis examined and that in most cases the majority of all eosinophils expressed both TGF-alpha and TGF-beta 1. These results suggest that production of TGF-alpha and TGF-beta 1 by the infiltrating eosinophils may contribute to some of the pathologic changes observed in nasal polyposis, such as thickening of the epithelial basement membrane, stromal fibrosis, angiogenesis, and epithelial and glandular hyperplasia.

Topics: Aniline Compounds; Eosinophils; Fluorescence; Fluorescent Dyes; Humans; Immunohistochemistry; In Situ Hybridization; Nasal Polyps; Proteins; Rhodamines; RNA, Messenger; Transforming Growth Factor alpha; Transforming Growth Factor beta