Expression of SOCS1 and SOCS3 Is Altered in the Nasal Mucosa of Patients with Mild and Moderate/Severe Persistent Allergic Rhinitis

Kim, Tae Hoon; Kim, Kihyoung; Park, Se Jin; Lee, Jun Young; Hwang, Jae Woong; Park, Sang Heon; Yum, Gun Hwee; Lee, Sang Hag

doi:10.1159/000333103

Cited by 18 publications

(14 citation statements)

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“…It blocks the phosphorylation of STAT6 through inhibiting JAK activity, and has been identified as a negative feedback regulator of the JAK/STAT6 pathway . Mucosal SOCS1 is increased in patients with AR and asthma compared with healthy controls . The present study results proved consistent with published data showing that IL‐13 or IL‐17A stimulation upregulated SOCS1 expression in airway epithelial cells .…”

Section: Discussionsupporting

confidence: 92%

Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

Wang

Zhu

et al. 2019

Int Forum Allergy Rhinol

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Background: Interleukin (IL)-17A is involved in the pathogenesis of allergic rhinitis (AR). Increased expression of IL-17A is correlated with disease severity and nasal eosinophilia. However, the molecular mechanisms by which IL-17A contributes to T-helper 2 cytokine IL-13-driven pathology in AR remain unclear. We sought to obtain mechanistic insight into how IL-17A and IL-13 regulate the epithelial production of eotaxin-3 representing eosinophilic inflammation in AR. Methods:Human nasal epithelial cells (HNECs) from AR patients were cultured and stimulated with IL-17A, IL-13, or IL-17A and IL-13. Phosphorylated signal transducer activator of transcription 6 (p-STAT6) and suppressor of cytokine signaling 1 (SOCS1) in HNECs were assayed using Western blo ing. Immunocytochemistry was used to determine p-STAT6-positive expression in the cells. Eotaxin-3 expression in the cells and culture supernatants was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Results:Stimulation with IL-13 alone induced STAT6 phosphorylation and promoted p-STAT6 nuclear translocation, leading to eotaxin-3 production by HNECs. These effects were further enhanced by cotreatment with IL-13 and IL-17A, whereas IL-17A alone had no impact on STAT6 or eotaxin-3 expression. Incubation with IL-17A or IL-13 increased the level of SOCS1 protein in the cells, whereas the addition of IL-17A a enuated IL-13-induced SOCS1 expression.Conclusion: IL-17A potentiated IL-13-driven STAT6 activation through the downregulation of SOCS1 expression, leading to enhancement of eotaxin-3 production by HNECs. These factors contributed to eosinophilic inflammation in AR. C 2019 ARS-AAOA, LLC. Key Words:allergic rhinitis; interleukin-17A; interleukin-13; eotaxin-3; signal transducer activator of transcription 6; suppressor of cytokine signaling 1 How to Cite this Article: Wang WW, Zhu K, Yu HW, Pan YL. Interleukin-17A potentiates interleukin-13-induced eotaxin-3 production by human nasal epithelial cells from patients with allergic rhinitis. Int Forum Allergy Rhinol. 2019;9:1327-1333.A llergic rhinitis (AR) is a chronic inflammatory disease with a prevalence of 10%-40%. 1 CD4 + T-helper (Th) cells play a vital role in local mucosal immune responses of allergic airway diseases. 2 AR has long been hypothesized as the result of dysregulation of the balance between Th1 and

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Section: Discussionsupporting

confidence: 92%

Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

Wang

Zhu

et al. 2019

Int Forum Allergy Rhinol

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“…SOCS1 and SOCS3 mRNA and protein expression was significantly increased in the nasal mucosa and PBMCs of patients with mild and moderate/severe persistent AR compared with healthy controls [36]. In our study, SOCS1 and SOCS3 mRNA were also highly expressed in the nasal mucosa and PBMCs in AR patients.…”

Section: Discussionsupporting

confidence: 63%

SOCS3 Is Upregulated and Targeted by miR30a-5p in Allergic Rhinitis

Zhao¹,

Wang²,

Yao³

et al. 2018

Int Arch Allergy Immunol

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Background: Suppressor of cytokine signaling 1 (SOCS1) and SOCS3 play important roles in T helper cell differentiation, which is involved with the pathologic mechanisms of allergic rhinitis (AR). The aim of this study was to evaluate the expression of SOCS1 and SOCS3 in AR and find their regulatory microRNAs (miRNAs) to provide a basis for the treatment of AR. Methods: The expression of SOCS1 and SOCS3 were analyzed by real-time PCR, immunohistochemistry, and Western blot. The correlative regulatory miRNAs were detected by real-time PCR. Luciferase assays and AR mouse model experiments were applied to identify correlative miRNAs that target SOCS3. Results: SOCS1 and SOCS3 mRNA were upregulated in the nasal mucosa and peripheral blood mononuclear cells of AR compared with controls. The expression of SOCS3 protein was significantly increased in the nasal mucosa of AR. The immunohistochemical staining results showed that SOCS3 was similarly localized in the superficial epithelium, submucosal glands, and vascular endothelium in the nasal mucosa of AR subjects and controls. However, SOCS3 protein was especially localized in the inflammatory cells, such as eosinophils, monocytes, and lymphocytes. Conclusions: SOCS3 was targeted by miR30a- 5p in AR. Further study should be performed to identify the regulatory effect of miR30a-5p in AR, which may provide insights into a new therapeutic strategy.

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“…24 Interleukin-13 also plays a vital role in the regulation of allergic illness pathogenesis via amplification of immediate hypersensitivity. 8,11 Interleukin-5 is responsible for infiltration of eosinophilia in the airway, which leads to late-phase allergic response. 22,25 Furthermore, clinically, it has been documented that patients with AR are associated with elevated levels of IL-17 in nasal mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…Studies suggested that balance between Th1 cells and Th2 cells plays a vital role in the maintenance of the immune health, and its dysregulation leads to the induction of allergic responses. 8,9…”

Section: Introductionmentioning

confidence: 99%

Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Chen

Yan

2020

Dose-Response

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Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential.Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications.Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 mL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 mL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction (P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly (P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited (P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and b-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-g in nasal lavage fluid were significantly decreased (P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-kB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited (P < .05) by apigenin. It also significantly ameliorated (P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA.Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-kB) and activation of Th1 response (IFN-g and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

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Expression of SOCS1 and SOCS3 Is Altered in the Nasal Mucosa of Patients with Mild and Moderate/Severe Persistent Allergic Rhinitis

Cited by 18 publications

References 50 publications

Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

SOCS3 Is Upregulated and Targeted by miR30a-5p in Allergic Rhinitis

Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

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