scholarly journals The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma

2016 ◽  
Vol 84 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Marcelina Koćwin ◽  
Mateusz Jonakowski ◽  
Marcelina Przemęcka ◽  
Jan Zioło ◽  
Michał Panek ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Signalling Pathway

scholarly journals Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Prieto-Peña ◽  
Sara Remuzgo-Martínez ◽  
Fernanda Genre ◽  
Verónica Pulito-Cueto ◽  
Belén Atienza-Mateo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Disease Onset ◽  
Immunoglobulin A ◽  
Genetic Network ◽  
Signalling Pathway ◽  
Immune Mediated ◽  
Increased Risk ◽  
Genotype And Allele Frequencies ◽  
Immunoglobulin A Vasculitis

AbstractCytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

scholarly journals The role of Notch ligand, Delta-like ligand 4 (DLL4), in cancer angiogenesis—implications for therapy

2021 ◽  
Author(s):  
Marlena Brzozowa-Zasada
Keyword(s):  
Cancer Therapy ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Gamma Secretase ◽  
Tumour Angiogenesis ◽  
Notch Signalling Pathway ◽  
Expression Levels ◽  
Blocking Agents ◽  
Anti Cancer

Summary Background It is generally accepted that angiogenesis is a complex and tightly regulated process characterized by the growth of blood vessels from existing vasculature. Activation of the Notch signalling pathway affects multiple aspects of vascular development. One of the components of the Notch signalling pathway, Delta-like ligand 4 (DLL4), has recently appeared as a critical regulator of tumour angiogenesis and thus as a promising therapeutic target. Methods This review article includes available data from peer-reviewed publications associated with the role of DLL4 in cancer angiogenesis. Searches were performed in PubMed, EMBASE, Google Scholar and Web of Science using the terms “tumour angiogenesis”, “DLL4”, “Notch signalling” and “anti-cancer therapy”. Results The survival curves of cancer patients revealed that the patients with high DLL4 expression levels had significantly shorter survival times than the patients with low DLL4 expression. Moreover, a positive correlation was also identified between DLL4 and VEGF receptorsʼ expression levels. It seems that inhibition of DLL4 may exert potent growth inhibitory effects on some tumours resistant to anti-VEGF therapies. A great number of blocking agents of DLL4/Notch signalling including anti-DLL4 antibodies, DNA vaccination, Notch antibodies and gamma-secretase inhibitors have been studied in preclinical tumour models. Conclusion DLL4 seems to be a promising target in anti-cancer therapy. Nevertheless, the careful evaluation of adverse effects on normal physiological processes in relation to therapeutic doses of anti-DLL4 drugs will be significant for advancement of DLL4 blocking agents in clinical oncology.

The role of systemic corticosteroids in severe asthma and new evidence in their management and tapering

2021 ◽  
Author(s):  
Francesco Menzella ◽  
Giulia Ghidoni ◽  
Matteo Fontana ◽  
Silvia Capobelli ◽  
Francesco Livrieri ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Systemic Corticosteroids ◽  
New Evidence

scholarly journals The role of kinases in the Hedgehog signalling pathway

EMBO Reports ◽  
2008 ◽  
Vol 9 (4) ◽  
pp. 330-336 ◽  
Author(s):  
Reid A Aikin ◽  
Katie L Ayers ◽  
Pascal P Thérond
Keyword(s):  
Signalling Pathway ◽  
Hedgehog Signalling ◽  
Hedgehog Signalling Pathway

scholarly journals Pharmacological Rationale for Targeting IL-17 in Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Experimental Models ◽  
Airflow Limitation ◽  
Interleukin 17 ◽  
Asthma Phenotype ◽  
T Helper 2 ◽  
Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

scholarly journals Severe eosinophilic bronchial asthma: new therapeutic options

2018 ◽  
pp. 44-52 ◽  
Author(s):  
N. M. Nenasheva
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Asthma ◽  
Bronchial Asthma ◽  
Biological Agents ◽  
Therapeutic Options ◽  
Clinical Use ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

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