Lung function, airway and peripheral basophils and eosinophils are associated with molecular pharmacogenomic endotypes of steroid response in severe asthma.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184433 | GEO | 2022/06/09
REPOSITORIES: GEO
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Project description:IntroductionAsthma is a complex disease with heterogeneous expression/severity. There is growing interest in defining asthma endotypes consistently associated with different responses to therapy, focusing on type 2 inflammation (Th2) as a key pathological mechanism. Current asthma endotypes are defined primarily by clinical/laboratory criteria. Each endotype is likely characterised by distinct molecular mechanisms that identify optimal therapies.MethodsWe applied unsupervised (without a priori clinical criteria) principal component analysis on sputum airway cells RNA-sequencing transcriptomic data from 19 asthmatics from the Severe Asthma Research Program at baseline and 6-8 weeks follow-up after a 40 mg dose of intramuscular corticosteroids. We investigated principal components PC1, PC3 for association with 55 clinical variables.ResultsPC3 was associated with baseline Th2 clinical features including blood (rank-sum p=0.0082) and airway (rank-sum p=0.0024) eosinophilia, FEV1 change (Kendall tau-b R=-0.333 (-0.592 to -0.012)) and follow-up FEV1 albuterol response (Kendall tau-b R=0.392 (0.079 to 0.634)). PC1 with blood basophlia (rank-sum p=0.0191). The top 5% genes contributing to PC1, PC3 were enriched for distinct immune system/inflammation ontologies suggesting distinct subject-specific clusters of transcriptomic response to corticosteroids. PC3 association with FEV1 change was reproduced in silico in a comparable independent 14-subject (baseline, 8 weeks after daily inhaled corticosteroids (ICS)) airway epithelial cells microRNAome dataset.ConclusionsTranscriptomic PCs from this unsupervised methodology define molecular pharmacogenomic endotypes that may yield novel biology underlying different subject-specific responses to corticosteroid therapy in asthma, and optimal personalised asthma care. Top contributing genes to these PCs may suggest new therapeutic targets.
| S-EPMC9016241 | biostudies-literature
Project description:Yorkshire pigs received untreated unilateral ACL transection through a medial arthrotomy (INJ, n=6), transection with immediate injection of 20mg triamcinolone acetonide (TRI, n=6) or no surgery (CON, n=6). Synovial membranes were harvested two weeks after the injury in the lateral knee joint compartment. The whole biopsy was homogenised for RNA extraction. The objective of the experiment was to test if intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection and to characterize the synovial response using the described perturbations in combination with a functional genomics approach.
2016-01-29 | E-MTAB-4294 | biostudies-arrayexpress
Project description:Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. Gene expression changes of human trabecular meshwork cells, TM 86 and TM 93, due to treatment with dexamethasone (Dex), fluocinolone acetonide (FA), and triamcinolone acetonide (TA).
2010-02-15 | GSE16643 | GEO
Project description:Gene expression profiling was performed on sputum samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes. Sputum samples were collected from asthmatics and healthy controls and subjected to expression profiling using Affymetrix HG-U133Plus2.0 microarrays.
2015-10-23 | E-GEOD-41863 | biostudies-arrayexpress
Project description:Transcriptome landscape of HeLa response upon triamcinolone acetonide
| PRJNA475732 | ENA
Project description:Tissue-resident memory T (TRM) cells are detrimental in numerous chronic inflammatory diseases, including allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease. We assessed the impact of a standard glucocorticosteroid treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal TRM cells in ACD.
2023-08-31 | GSE216725 | GEO
Project description:Ten male 4get mice were infected with N. brasiliensis and single-cell suspensions of total lung tissue were prepared 9 days after infection. Cells were stained for CD3, CD19, c-kit and CCR3 and sorted for CD3-CD19-c-kit-GFP+CCR3+SSChi (eosinophils) and CD3-CD19-c-kit- GFP+CCR3-SSClo (basophils) using a MoFlo high-speed cell sorter (Cytomation, Fort Collins, CO). Total RNA was isolated from 2 x 106 eosinophils and 1.75 x 105 basophils using the Total RNA Isolation Kit (Fluka, Buchs, Switzerland) and amplified by two rounds of in vitro transcription using the Amino Allyl MessageAmpTM aRNA kit (Ambion, Austin, TX). Universal Mouse Reference RNA (#740100; Stratagene, La Jolla, CA) was amplified in the same way. Aminoallyl-UTP was incorporated during the second round of amplification and 5 µg of amplified RNA was coupled to Cy3 and Cy5 fluorescent dyes (CyScribeTM dye labeling kit, Amersham Biosciences, Peapack, NJ). Probes were hybridized to spotted glass oligonucleotide (70-mer) arrays which cover just over 16,400 unique genes (Mouse Genome Set Version 2.0, Qiagen, Germany). The arrays were prehybridized in 1% BSA (Invitrogen), 5 x SSC, 0.1% SDS for 2 hr at 42°C, washed in water and hybridized with the Cy3/Cy5-labeled probes in 2.8 x SSC, 0.2% SDS, 0.6 mg/ml Cot-1 DNA (Invitrogen), and 0.8 mg/ml yeast tRNA, at 63°C for 45 hr. Slides were washed sequentially in 0.03%SDS/1 x SSC, 0.2 x SSC and 0.05 x SSC, dried and scanned on an Axon 4000B scanner using Genepix 3.0 software (Axon Instruments, Inc.). Data were normalized using the R package Bioconductor software and ?lowess? normalization on the pixel medians without background subtraction (Ihaka and Gentleman, 1996). Keywords = Eosinophils Keywords = Basophils Keywords = Nippostrongylus Keywords = Lung Keywords = Type 2 immunity Keywords: other
2004-02-21 | GSE984 | GEO
Project description:Gene expression profiling was performed on sputum samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes.
2015-10-23 | GSE41863 | GEO
Project description:Hypertrophic scar (HS) is a skin lesion due to abnormal wound healing after skin injury; histologically, HS is characterized by deposition of excessive amounts of the extracellular matrix and collagen produced by wound healing-induced proliferative fibroblasts. Clinically, HS management includes surgical resection of HS, topical glucocorticoid therapy or drug injections, pressure therapy, fractional carbon dioxide laser therapy, and cryotherapy. In terms of non-surgical therapy, glucocorticoids (like Triamcinolone acetonide, a synthetic corticosteroid medication used topically to treat various skin conditions) was able to effectively inhibit HS formation safely for decades. The effects of glucocorticoids may either be due to its anti-inflammatory, anti-allergenic and immunomodulatory effects or activate fatty acids metabolism by promotion of lipid accumulation in fibroblasts. However, it is no clear why and how glucocorticoids-upregulated fatty acid metabolisms benefit in HS treatment and prevention.And it remains to be defined how altered microRNAs regulated-fatty acid metabolism involved in pathological scars.
2023-02-25 | GSE225646 | GEO
Project description:Background: A subset of asthmatics does not respond to steroid therapy and therefore is at risk for escalation of disease severity. The cause of corticosteroid resistant (CR) asthma is unknown. Gene microarray technologies have the potential to substantiate new hypotheses regarding the etiology of corticosteroid resistance. Methods: Gene microarray analysis was performed with bronchoalveolar lavage (BAL) cells of CR and corticosteroid sensitive (CS) asthmatics. Increased gene expression was verified with real time PCR and at the protein level by ELISA. Findings: Microarray analyses demonstrated significantly higher levels (over two-fold increase, p<0.05) of TNF-alpha, IL-1alpha, IL-1beta, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, CCL20 gene expression in BAL cells of CR than CS asthmatics. These findings, confirmed by RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively-activated macrophages, Arginase I and CCL24, were decreased in CR asthmatics. Genes associated with activation of the LPS signaling pathway (EGR1, DUSP2, MAIL, TNFAIP3) were significantly elevated in CR BAL samples (p<0.05). CR asthmatics had significantly higher amounts (1444.0±457.3 pg per mg of total protein) of LPS in BAL fluid than CS asthmatics (270.5±216.0 pg; p<0.05). Prolonged exposure to LPS induced functional steroid resistance to dexamethasone (DEX) in normal monocytes, demonstrated by persistently elevated IL-6 levels in the presence of DEX. Interpretation: Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from CR asthmatics suggest that LPS exposure may contribute to CR asthma. Keywords: Disease state analysis
2009-06-22 | GSE7368 | GEO