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

Linke, Robert; Pries, Ralph; Könnecke, Michael; Bruchhage, Karl‐Ludwig; Böscke, Robert; Gebhard, Maximilian; Wollenberg, Barbara

doi:10.2500/ajra.2015.29.4170

Cited by 3 publications

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“…The receptors for these cytokines activate JAKs by phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, suggesting that the JAK/STAT pathway is involved in the pathogenesis of chronic lower respiratory tract inflammatory diseases [7,9,10]. In a study on JAK/STAT signaling in CRS, Linke et al revealed distinct expression and activation of STAT5b in nasal polyps, suggesting that STAT5b may contribute to the development of nasal polyps [11]. Moreover, dupilumab blocks both IL-4 and IL-13 signaling in treatment for patients with moderate to severe CRSwNP, thereby modulating downstream STAT6 or STAT3 phosphorylation via inactivation of JAK1 or JAK2; subsequently inflammation and tissue remodeling is able to be controlled and regulated [12].…”

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confidence: 99%

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

et al. 2021

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Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Lam et al 3 used sinus mucosal samples to demonstrate increased IL-25 and IL-33 expression, but not TSLP expression, in patients with chronic rhinosinusitis, nasal polyps, and >10 eosinophils/high power field, in a comparison study with normal control tissue. Linke et al, 4 in another study using human samples, this time nasal polyps and inferior turbinate tissue, found that STAT5b, but not STAT5a, is activated compared to controls in patients with chronic rhinosinusitis and nasal polyps. Finally, Esmaeilzadeh et al 5 identified genetic variabilities of major histocompatibility complex class II for patients with aspirin exacerbated respiratory disease, suggesting a role for T cell activation in the pathophysiology of this disease process.…”

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Advancing the Field of Rhinology and Allergy

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The May/June issue of the American Journal of Rhinology & Allergy contains several articles that advance the field of rhinology and allergy. This editorial will provide a high level summary of the articles contained in this issue-be sure to examine the articles in more depth on the following pages.Several studies in this issue focus on the pathophysiology of airway inflammation. Wang et al 1 studied the regulation of aquaporin-5, a channel protein important for fluid secretion in allergic inflammation. They tested the 4 concentrations of histamine on the expression of aquaporin-5 in human nasal epithelial cells, findings a dose dependent decrease in expression. They further discovered that the downregulation of aquaporin by histamine occurs via inhibition of the cyclic adenosine monophosphate-responsive element binding protein. Choi et al 2 found that Asian sand dust, generated from the deserts in China, are capable of inducing MUCH8 and MUC5b expression via TLR-4 dependent signaling pathways. These findings were derived from experiments using human nasal epithelial cells. Asian sand dust may be an important environmental trigger for TLR-4 pathway expression and subsequent promotion of airway inflammation. Lam et al 3 used sinus mucosal samples to demonstrate increased IL-25 and IL-33 expression, but not TSLP expression, in patients with chronic rhinosinusitis, nasal polyps, and Ͼ10 eosinophils/high power field, in a comparison study with normal control tissue. Linke et al, 4 in another study using human samples, this time nasal polyps and inferior turbinate tissue, found that STAT5b, but not STAT5a, is activated compared to controls in patients with chronic rhinosinusitis and nasal polyps. Finally, Esmaeilzadeh et al 5 identified genetic variabilities of major histocompatibility complex class II for patients with aspirin exacerbated respiratory disease, suggesting a role for T cell activation in the pathophysiology of this disease process.One study focused on sinonasal tumor pathophysiology. Jung et al 6 studied expression of the Wnt signaling pathway to better understand the mechanism involved in the malignant transformation of sinonasal inverted papillomas. Their findings suggest several Wnt pathway signaling proteins, including ␤-catenin, cyclin D1, and Dvl-1, are associated with malignant transformation.Two studies analyzed imaging results as a means to better understand challenging diagnostic and management issues in rhinology. Craig and Goyal 7 analyzed images of patients who sustained sphenoid fractures and found that CSF leaks occurred in 9% and blunt carotid injury occurred in just 2% of sphenoid fractures. They also found a significant association between sphenoid roof fractures and CSF leak and that penetrating issues were strongly associated with CSF leak. Lin et al 8 describe the use of volumetric analysis for assessment of orbital volume in patients with chronic maxillary atelectasis, also called silent sinus syndrome. They concluded that expansion of maxillary sinus and decrease in orbit volume ca...

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STAT5 expression correlates with recurrence and survival in melanoma patients treated with interferon-α

et al. 2018

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Interferons (IFN) have a direct growth-inhibiting effect on tumor cells through Janus kinase-dependent activation of the transcription factor signal transducer and activator of transcription (STAT1). In vitro, signaling through STAT5 has been demonstrated to counteract this effect and lead to IFN resistance of melanoma cell lines. In 32 patients treated with IFN-α in an adjuvant setting, we investigated paraffin-embedded tumor tissue from primary melanomas and melanoma metastases for expression of STAT3 and STAT5, by immunohistochemistry, and for expression of phosphorylated signaling transduction activating transcription factor (pSTAT)3 and pSTAT5, by immunofluorescence. Tumor cell expression levels of these proteins were correlated with patient characteristics and clinical outcomes. The patient cohort consisted of 12 (37.5%) patients at AJCC stage I/II (primary melanoma) and 20 (62.5%) at stage III/IV (metastatic melanoma). Recurrence was observed for 25 (78.1%) either during or after IFN-α therapy. χ Correlation of staining intensities with clinical data revealed association of pSTAT3 and STAT5 expression with sex (P=0.003 and 0.016, respectively) and of STAT3 with tumor stage (P=0.019). Recurrence of melanoma was found to be associated with high STAT5 expression (P=0.017). Multivariable regression analysis revealed STAT5 expression as an independent factor for predicting progression-free survival (P<0.0001) and overall survival (P=0.022). In summary, high expression of STAT5 correlated with melanoma recurrence and survival of patients treated with IFN-α in the adjuvant setting. Recently, it has been suggested that mutations of Janus kinases are involved in resistance to immune checkpoint blocker treatments implying a possible role of STAT5 for immune checkpoint resistance.

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

Abstract: Analysis of these data indicates distinct expression and activation of STAT5a and STAT5b in nasal polyps, particularly the activation of STAT5b. It is possible that STAT5b may contribute to the development of nasal polyps.

Cited by 3 publications

References 34 publications

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

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

Advancing the Field of Rhinology and Allergy

STAT5 expression correlates with recurrence and survival in melanoma patients treated with interferon-α

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