PI3K and ERK1/2 kinase inhibition potentiate protease inhibitor to attenuate allergen induced Th2 immune response in mouse

Saw, Sanjay; Arora, Naveen

doi:10.1016/j.ejphar.2016.02.050

Cited by 9 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inactivation of PI3Kp110δ in Treg disables tumor-induced immune suppression and enables immune-mediated tumor regression in murine models (Ali et al, 2014). PI3K is also identified as a nodal control point for Treg homeostasis and stability (Huynh et al, 2015), and has been for -Fenoll et al, 2016;Chang et al, 2007;Khadem et al, 2017;Saw & Arora, 2016). In accordance with these publications, our Tregs from each group and Teff were cocultured at a ratio of 3:1 for 72 hr in the presence of IL-2 and anti-CD28 antibodies.…”

Section: The Pi3k Inhibitors Induced Treg/th17 Rebalance In Sarcoidmentioning

confidence: 74%

“…Inhibition of PI3K increased the ratio of Treg to effector populations, tipping the balance from autoreactive‐T‐cells to Treg, thus conferring protection against autoimmune diabetes (Azzi et al, ). Inhibition of PI3Kp110α, δ, or γ improves immune regulation, and is an effective therapeutic approach in rheumatoid arthritis, experimental leishmaniasis, atherosclerosis, and allergen induced airway response (Aragoneses‐Fenoll et al, ; Chang et al, ; Khadem et al, ; Saw & Arora, ). In accordance with these publications, our data show a direct role for PI3K inhibition in Treg's differentiation and suppressive function in SodA‐induced sarcoidosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Phosphoinositide 3‐kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis

Zhang

Dai

Jin

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Sarcoidosis is a systemic granulomatous disease associated with Th1/ regulatory T cells (Treg) paradigm. PI3K/Akt signaling, critical for maintaining Treg's homeostasis, is aberrantly activated in sarcoidosis patients. Here we tested the role of the PI3K inhibitors, LY294002 and BKM120, in immune modulation in experimental pulmonary sarcoidosis, concerning Th1/Th17/Treg immune profile detected by fluorescence-activated cell sorting analysis or quantitative polymerase chain reaction, as well as the effect on Treg's suppressive functions. Our investigation showed abnormal activation of PI3K/Akt signaling both in lung and Treg in pulmonary sarcoidosis, along with decreased frequency and damaged function of Treg. Blockage of PI3K suppressed this signaling in Treg, rebalanced Th1/Treg, inhibited the production of inflammatory cytokines, and enhanced Treg's function. These results demonstrate the key role of the PI3K/Akt signaling in regulating Th1/Th2 rebalances and indicates that PI3K/Akt signaling is critical for the optimal Treg responses in pulmonary sarcoidosis. Thus, PI3K inhibitors have potential for therapeutic translation, and can be candidate for add-on drugs to treat pulmonary sarcoidosis.

show abstract

Section: The Pi3k Inhibitors Induced Treg/th17 Rebalance In Sarcoidmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Phosphoinositide 3‐kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis

Zhang

Dai

Jin

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…26, 27 The release of these inflammatory mediators are consequences of the complex interplay of PI3K/ERK1/2 kinase. 28 Therefore, we explored the possible involvement of CALCB mutations in the trypsin-induced AIP. Our results indicated that trypsin co-expressed with PAR2 in the pancreatic tissues neither from the patients with CALCB mutations nor that of the wild-type, it maybe supporting the effects of trypsin in the AIP.…”

Section: Discussionmentioning

confidence: 99%

CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis

Liu

Chen

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present study applied whole-exome sequencing (WES) to determine the underlying etiology and revealed novel missense splice region variants, CALCB c.88T>C (p.Ser30Pro) and IR [1]-mutants, in 2 of the 3 families and 2 of 26 unrelated patients with type 1 AIP. In vitro, both of the mutants displayed decreased βCGRP, ERK1/2 phosphorylation, and co-localized with endoplasmic reticulum and Golgi apparatus. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of AIP.

show abstract

“…development of bronchial asthma by reducing inflammatory responses (14). In another study, ERK1/2 kinase inhibition was found to be able to attenuate Th2 immune response induced by allergens in mouse model (15). Based on our knowledge, the involvement of ERK1/2 kinase in the development of adenoid hypertrophy still has not yet been reported.…”

Section: Discussionmentioning

confidence: 85%

CYSLTR1 promotes adenoid hypertrophy by activating ERK1/2

Gao

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

Cysteinyl leukotriene receptor 1 (CYSLTR1) serves a pivotal role in allergic reactions, which is one of the main causes of adenoid hypertrophy. The present study aimed to investigate the function of CYSLT1 within adenoid hypertrophy. A total of 40 patients with adenoid hypertrophy were recruited between January 2014 and January 2016 at the Children's Hospital of Hebei Province, China. The patients were divided into either the mild-moderate group or the severe group according to their disease severity. The expression of CYSLT1 in the adenoid tissue and whole blood of all patients and healthy controls was detected by reverse transcription-quantitative polymerase chain reaction. Associations between the expression level of CYSLT1 and the clinical characteristics of patients were analyzed. Primary human adenoid epithelial cells (HAECs) with CYSLT1 knockdown and overexpression were constructed. The levels of extracellular signal-regulated kinase (ERK)2 and phosphorylated-ERK1/2 in adenoid tissue and HAECs were detected by western blot analysis. The expression of CYSLT1 in adenoid tissue and whole blood of all patients with adenoid hypertrophy was significantly higher compared with the healthy controls (P<0.05). In addition, the expression level of CYSLT1 was significantly higher in the severe group compared with the mild-moderate group (P<0.05). The highest level of p-ERK1/2 in adenoid tissue was observed in the severe group, followed by the mild-moderate group and then the control group (P<0.05). CYSLT1 expression was positively associated with the severity of disease. CYSLT1 knockdown significantly decreased the level of p-ERK1/2 in HAECs (P<0.05), while CYSLT1 overexpression significantly increased the level of p-ERK1/2. It was concluded that CYSLT1 may contribute to the progression of adenoid hypertrophy by activating ERK1/2.

show abstract

PI3K and ERK1/2 kinase inhibition potentiate protease inhibitor to attenuate allergen induced Th2 immune response in mouse

Cited by 9 publications

References 40 publications

Phosphoinositide 3‐kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis

Phosphoinositide 3‐kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis

CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis

CYSLTR1 promotes adenoid hypertrophy by activating ERK1/2

Contact Info

Product

Resources

About