Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma

Kobayashi, Yoshiki; Kanda, Akira; Yun, Yasutaka; Van, Bui Dan; Suzuki, Kensuke; Sawada, Sunsuke; Asako, Mikiya; Iwai, Hiroshi

doi:10.3390/biom10020326

Cited by 14 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 152 PP2A regulated glucocorticoid receptor nuclear translocation and corticosteroid sensitivity, possibly by dephosphorylation of glucocorticoid receptor at Ser226 and dephosphorylation of upstream JNK1 in severe asthma. 153 , 154 PP2A was shown to control mast cell degranulation through dephosphorylation of Thr567 in the Ezrin/Radixin/Moesin signaling pathway. 155 , 156 …”

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage. On the other hand, inflammation can also initiate tissue damage repair and maintain normal tissue function by resolving injury and restoring homeostasis. These opposing functions emphasize the significance of accurate regulation of inflammatory homeostasis to ameliorate inflammation-related diseases. Potential mechanisms involve protein phosphorylation modifications by kinases and phosphatases, which have a crucial role in inflammatory homeostasis. The mechanisms by which many kinases resolve inflammation have been well reviewed, whereas a systematic summary of the functions of protein phosphatases in regulating inflammatory homeostasis is lacking. The molecular knowledge of protein phosphatases, and especially the unique biochemical traits of each family member, will be of critical importance for developing drugs that target phosphatases. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of all protein phosphatases in inflammation-related diseases, as well as their potential inhibitors or activators that can be used in therapeutic interventions in preclinical or clinical trials. We provide an integrated perspective on the current understanding of all the protein phosphatases associated with inflammation-related diseases, with the aim of facilitating the development of drugs that target protein phosphatases for the treatment of inflammation-related diseases.

show abstract

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…MIP-1β has also been found associated with reduced response to nasal corticosteroid sprays in CRS patients with concomitant asthma (35) .…”

Section: Discussionmentioning

confidence: 96%

Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers

Guo¹,

Liao²,

Jx³

et al. 2020

Rhin

View full text Add to dashboard Cite

Background: Previous studies have been limited to the utility of clinical features and invasive nasal mucosal biomarkers in the prediction of chronic rhinosinusitis (CRS) outcomes. This study aimed to identify noninvasive biomarkers associated with difficultto-treat CRS, enabling physicians to subgroup patients into risk groups for poor outcome before surgery. Methods: Three hundred and nine CRS patients undergoing endoscopic sinus surgery were finally enrolled. Patients treated with oral or intranasal glucocorticoids within 3 months or 1 month before surgery, respectively, were excluded. Baseline clinical characteristics, nasal secretions and peripheral blood samples were collected before surgery. The protein levels of 39 biological markers were detected by the Bio-Plex suspension chip method. Classification and regression tree analysis was applied to establish prediction model for difficult-to-treat CRS determined one year after surgery. A random forest algorithm was used to confirm the discriminating factors that formed the classification tree. Results: In the cohort with nasal secretion sample (n = 189), 21% of CRS patients were diagnosed as difficult-to-treat after 1 year of follow-up. Nasal secretion CCL17 level, hyposmia score, allergic rhinitis comorbidity, and nasal secretion MIP-1β level were found important predictors of difficult-to-treat CRS. A classification tree separated patients into 5 subgroups leading to an overall predictive accuracy of 94%. However, none of the plasma biological markers were associated with difficult-to-treat CRS in the cohort with blood sample (n = 128). Conclusions: Patients with difficult-to-treat-CRS were characterized by higher nasal secretion levels of CCL17 and MIP-1β, severe hyposmia and concomitant allergic rhinitis. The classification tree could be useful to identify patients with high risk of poor outcome prior to surgery and offer more personalized interventions. However, since only patients without preoperative steroid treatments were included in this study, the generalization of our predictive model in other patient populations should be considered with caution.

show abstract

“…Although CCL4 was mainly associated with mononuclear cells and released from them [ 11 , 13 ], activated eosinophils are also sources, especially in airway inflammation. Furthermore, we preliminarily confirmed that CCL4 was highly expressed in sinonasal epithelial cells from patients with ECRS [ 9 ].…”

Section: Introductionmentioning

confidence: 88%

“…Importantly, local corticosteroid sensitivity in patients with severe asthma and ECRS is markedly reduced, thus the conditions are difficult to control. As we previously indicated, co-incubation with eosinophils reduced corticosteroid sensitivity in bronchial epithelial cells; eosinophils in the airway induced corticosteroid resistance [ 9 ]. Therefore, it is important to elucidate mechanisms underpinning eosinophil accumulation in airways to inhibit eosinophil infiltration and restore corticosteroid sensitivity.…”

Section: Introductionmentioning

confidence: 96%

CCL4 Functions as a Biomarker of Type 2 Airway Inflammation

et al. 2022

Self Cite

View full text Add to dashboard Cite

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils or eosinophil peroxidase (EPX). We examined serum chemokine (CCL4, CCL11, CCL26, and CCL17) and total IgE serum levels, fractionated exhaled nitrogen oxide (FENO), and CCL4 expression in nasal polyps in patients with severe ECRS and asthma. CCL4 was induced by TSLP under eosinophilic inflammation. Furthermore, CCL4 was released via TLR3 signaling, which was enhanced by TSLP. CCL4 was mainly located in nasal polyp epithelial cells, while serum CCL4 levels were reduced after dupilumab treatment. Serum CCL4 levels were positively correlated with FENO, serum IgE, and CCL17 levels. Thus, CCL4 released from epithelial cells via the innate immune system during type 2 airway inflammation may function as a useful biomarker for the condition.

show abstract

Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma

Cited by 14 publications

References 29 publications

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers

CCL4 Functions as a Biomarker of Type 2 Airway Inflammation

Contact Info

Product

Resources

About