Increased Activation and Differentiated Localization of Native and Phosphorylated STAT3 in Nasal Polyps

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease; the underlying mechanisms of cell signalling are not fully understood. STAT3 (signal transducer and activator of transcription 3) is a phosphokinase and a key signalling molecule implicated in cell cycle regulation. We studied the distribution and expression of STAT3 to examine the role of STAT3 in the pathogenesis of CRSwNP. Methods: We investigated tissue samples of the nasal polyps and inferior turbinate of patients with CRSwNP as well as samples of the inferior turbinate of subjects without chronic sinusitis. The expression levels of STAT3 and its activated form pSTAT3 were analysed using Western blotting, protein array, DNA microarray and immunohistochemistry. Results: No significant differences were found in STAT3-mRNA levels between the samples of nasal polyps and inferior turbinates of the same patient. However, the amount of pSTAT3 was increased in the polyp tissue compared to the inferior turbinates from both CRSwNP patients and control subjects (p < 0.01), indicating an activation of STAT3 in polyps. We identified a varying distribution pattern of pSTAT3; pSTAT3 was primarily found in superficial epithelial cells but not in the basal layer of the epithelium of the turbinate, whereas pSTAT3 was located in all layers of the epithelium of the polyp and mostly noted in the basal layer. Conclusions: Our results of the activation and varying localisation of STAT3 and its phosphorylated form in nasal polyps suggest that pSTAT3 plays a crucial role in the proliferative development of nasal polyps.

IL-19 Up-Regulates Mucin 5AC Production in Patients With Chronic Rhinosinusitis via STAT3 Pathway

“…STAT proteins are critical mediators of cytokine signaling among which STAT3 has been identified to be linked to tumorigenesis and inflammation (12, 36–38). Previous studies proposed that STAT3 and its phosphorylated form, P-STAT3, were mainly located in the superficial layer of the epithelium of CRSwNP patients, while hardly expressed in normal tissues (39, 40), similar to the expressions of IL-19 and MUC5AC observed in the present study. We wonder if the effect of STAT3 in IL-19, induced MUC5AC production.…”

Increased Phosphorylation of STAT5b, but not STAT5a, in Nasal Polyps

“…17 The results of this study are in accordance with the results of our own research concerning STAT3. 18 In contrast to our study, Wang et al 17 detected decreased levels of pSTAT5 compared with controls. However, Wang et al 17 examined polyps from Asian patients, and we examined polyps from Caucasian patients.…”

“…STAT1 is activated in nasal polyps compared with healthy nasal tissue, and its activation may be related to abnormalities in NO metabolism in CRSwNP. 14 STAT3 was found to be activated in four studies 15–18 and was described as downregulated in one report. 19 Corticosteroid treatment of patients with CRSwNP leads to decreased phosphorylated STAT3 (pSTAT3).…”

JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

“…A previous study indicated that IL-6 signaling may play a pathogenic role in CRSwNP [35]. In addition, p-STAT3 was found in both the superficial and basal layer of the epithelium of the polyps, which plays a crucial role in the proliferative development of nasal polyps [36]. Moreover, Lai et al in 2019 indicated that IL-19 may upregulate mucin production via the STAT3 pathway in CRS [37].…”