- |||||||||| [VIRTUAL] Different Doses of LPS Affect Macrophage Polarization and Alter the Asthma Phenotype () - Mar 14, 2021 - Abstract #ATS2021ATS_38;
In closer examination of IMs, M1 (CD86+CD206-) increased more in OH compared to OL whereas, M2 (CD86-CD206+) increased equally in both of OL and OH. CD86+CD206+ IMs, which showed good correlation with Th17, also increased in LPS dose-dependent fashion.Conclusion Macrophage polarization by different doses of LPS may play a key role in determining Th2/Th17 balance which result in distinct immunologic phenotypes of asthma.
- |||||||||| Journal: Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type 2 Cytokines and Rhinovirus. (Pubmed Central) - Mar 9, 2021
Collectively, these data demonstrate that Tollip restricts excessive IL-8 production in type 2 cytokine-exposed human airways during RV infection by promoting sST2 production and inhibiting IRAK1 activation. sST2 and IRAK1 may be therapeutic targets for attenuating excessive neutrophilic airway inflammation in asthma, especially during RV infection.
- |||||||||| navarixin (MK-7123) / Merck (MSD), Ligand
Journal: A Micro-Engineered Airway Lung-Chip Models Key Features of Viral-Induced Exacerbation of Asthma. (Pubmed Central) - Dec 16, 2020 Neutrophil transepithelial migration was greatest when viral infection was combined with IL-13 treatment, whereas treatment with MK-7123, a CXCR2 antagonist, reduced neutrophil diapedesis in all conditions...Our data suggest that IL-13 may impair the hosts' ability to mount an appropriate and coordinated immune response to rhinovirus infection. We also show that the Airway Lung-Chip can be used to assess the efficacy of modulators of the immune response.
- |||||||||| Journal: N-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2. (Pubmed Central) - Oct 21, 2020
Studies with primary lung epithelial cells also demonstrated that Chi3l1 inhibited while IL-13 stimulated the catalytic subunits (STT3A and STT3B) of the N-glycosylation inducing oligosaccharyltransferase (OST) complex. These studies demonstrate that N-glycosylation is a critical determinant of Chi3l1 and IL-13 binding to IL-13Rα2 and highlight the ability of Chi3l1 and IL-13 to alter key elements of the N-glycosylation apparatus in a manner that would augment their respective binding.
- |||||||||| [VIRTUAL] ANTI-INFLAMMATORY AND ANTIBACTERIAL POTENTIAL OF MEK1/2 INHIBITORS () - Oct 7, 2020 - Abstract #NACFC2020NACFC_467;
Preliminary results do not indicate that MEK1/2 inhibitors reduce the phagocytosis and killing abilities of macrophages. Addition of a MEK1/2 inhibitor compound to broth cultures of S. aureus inhibits growth, while growth of P. aeruginosa was not altered by addition of a MEK1/2 inhibitor compound.
- |||||||||| Xeljanz (tofacitinib) / Pfizer, Marche Polytechnic University
Journal: Attenuation of Dupuytren's fibrosis via targeting of the STAT1 modulated IL-13Rα1 response. (Pubmed Central) - Sep 17, 2020 We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren's as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease.
- |||||||||| Mucosta oral (rebamipide oral) / Otsuka, Acucela
Journal: Efficient RNP-Directed Human Gene Targeting Reveals SPDEF is Required for IL-13-Induced Mucostasis. (Pubmed Central) - Jul 29, 2020 In addition, targeting of SPDEF prevented IL-13-induced impairment of mucociliary clearance, which is likely to be an important contributor to airway obstruction, morbidity, and mortality in asthma. We conclude that direct delivery of sgRNA and rCas9 complexes allows for predictable and efficient gene targeting and enables mechanistic studies of disease-relevant pathways in primary HBECs.
- |||||||||| Xeljanz (tofacitinib) / Pfizer, Marche Polytechnic University
Journal: Attenuation of Dupuytren's fibrosis via targeting of the STAT1 modulated IL-13Rα1 response. (Pubmed Central) - Jul 24, 2020 We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren's as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease.
- |||||||||| [VIRTUAL] IL33 regulates airway neuronal plasticity in vitro (Channel 2) - Jul 15, 2020 - Abstract #ERS2020ERS_5040;
Increased neuronal density could be inhibited by anti-ST2 and is partially mediated via TrkB/BDNF. Importantly, patient data showed a correlation between IL1RL1 and TrkB, suggesting a critical role for IL33 in neuronal plasticity in asthma.
- |||||||||| [VIRTUAL] Epithelial MicroRNA-141 Regulates IL-13-Induced Airway Mucus Production (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_7375;
Proprietary AA blend increasing IL-13-induced decrease in sodium absorption and decreasing chloride secretion in HBEC could be used for treating hypersecretion in upper airways during allergy and asthma. We have identified a miRNA that regulates pathological airway mucus production in human cells and in mice and is amenable to therapeutic manipulation through an inhaled route.
- |||||||||| Mucosta oral (rebamipide oral) / Otsuka, Acucela
[VIRTUAL] MUC5AC Is Required for IL-13-Induced Mucostasis (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_7370; CRISPR targeting reduced MUC5AC production and rescued HBECs from IL-13-induced mucostasis. Therapies that could reduce MUC5AC would likely restore mucociliary transport and prevent mucus plugging in individuals with IL-13-driven type 2-high asthma.
- |||||||||| [VIRTUAL] IL-33 Regulates Airway Neuronal Plasticity In Vitro (ATS 2020 Virtual) - Jul 6, 2020 - Abstract #ATSI2020ATS-I_7312;
Conclusions IL-33 is a potential link between airway inflammation and airway neuronal plasticity, as IL-33 increased BDNF and TrkB expression and neuronal density, whereas IL-13 did not. Increased neuronal density could be inhibited by anti-ST2 and is partially mediated via BDNF as shown by anti-BDNF treatment, indicating that additional mechanisms play a crucial role in airway neuronal plasticity.
- |||||||||| Epithelial MicroRNA-141 Regulates IL-13-Induced Airway Mucus Production (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area J) - Mar 15, 2020 - Abstract #ATS2020ATS_10151;
Proprietary AA blend increasing IL-13-induced decrease in sodium absorption and decreasing chloride secretion in HBEC could be used for treating hypersecretion in upper airways during allergy and asthma. We have identified a miRNA that regulates pathological airway mucus production in human cells and in mice and is amenable to therapeutic manipulation through an inhaled route.
- |||||||||| Mucosta oral (rebamipide oral) / Otsuka, Acucela
MUC5AC Is Required for IL-13-Induced Mucostasis (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area J) - Mar 15, 2020 - Abstract #ATS2020ATS_10146; CRISPR targeting reduced MUC5AC production and rescued HBECs from IL-13-induced mucostasis. Therapies that could reduce MUC5AC would likely restore mucociliary transport and prevent mucus plugging in individuals with IL-13-driven type 2-high asthma.
- |||||||||| Interleukin-13 Promotes Changes in the Metabolism of Asymmetric Dimethylarginine (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area C) - Mar 15, 2020 - Abstract #ATS2020ATS_10082;
IL-13 modulates key regulatory enzymes leading to the intracellular accumulation of ADMA in airway epithelial cells. This provides a potential explanation for how allergic inflammation promotes ADMA accumulation in asthma, which may further inflammation by promoting further oxo-nitrosative stress.
- |||||||||| IL-33 Regulates Airway Neuronal Plasticity In Vitro (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area C) - Mar 15, 2020 - Abstract #ATS2020ATS_10080;
Inhibiting IL-33 function by blocking its receptor ST2/IL1RL1 abolished the effect, whereas, inhibiting BDNF using anti-BDNF only partially prevented the augmented neuronal network formation.ConclusionsIL-33 is a potential link between airway inflammation and airway neuronal plasticity, as IL-33 increased BDNF and TrkB expression and neuronal density, whereas IL-13 did not. Increased neuronal density could be inhibited by anti-ST2 and is partially mediated via BDNF as shown by anti-BDNF treatment, indicating that additional mechanisms play a crucial role in airway neuronal plasticity.
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