Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (n = 29); (2) ASD group without allergy/asthma (n = 29); (3) Allergy group (n = 30) and from typically developing age-matched control subjects (n = 28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation.
Essential management is to avoid cross-reacting cyclooxygenase 1 (COX-1) inhibitors along with use of highly selective COX-2 inhibitors and to maintain pharmacologic treatment depending on the severity of asthma and chronic rhinosinusitis.
Collectively, these findings suggest that COX-2 is a major gene related to cockroach allergen-induced oxidative stress and highlight a novel role of miR-155 in regulating the ROS-COX-2 axis in asthma.
Additionally, in the OVA-induced asthma model, the number of immune cells in the bronchoalveolar lavage fluid, the concentration of OVA-specific IgE, the infiltration of inflammatory cells, the bronchial thickness and the levels of the inflammatory mediators interleukin-4 (IL-4), IL-13 and COX-2 were significantly lower in the OVA + SEAC‑treated group compared with the OVA + vehicle‑treated group.
In this subnetwork, several receptors (EGFR, EGR1, ESR2, PGR), transcription factors (MYC, JAK), cytokines (IL8, IL6, IL1B), one chemokine (CXCL1), one kinase (SRC) and one cyclooxygenase (PTGS2) were described to be associated with inflammatory environment and steroid resistance in asthma.
Cyclooxygenase 2 (COX-2: official gene symbol - PTGS2) has long been regarded as playing a pivotal role in the pathogenesis of airway inflammation in respiratory diseases including asthma.
Cyclooxygenase-2 (COX-2) expression and PGE2 secretion from human airway smooth muscle cells (hASMCs) may contribute to β2-adrenoceptor hyporesponsiveness, a clinical feature observed in some patients with asthma. hASMCs from patients with asthma exhibit elevated expression of cytokine-responsive genes, and in some instances this is attributable to an altered histone code and/or microRNA expression.
The abundance of cyclooxygenase-2 (COX-2) and IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or miR-146b might modulate inflammatory mediator expression in airway smooth muscle thereby contributing to pathogenesis of asthma.
Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -765 G/C (OR 5.64; 95% CI 2.91-10.9 and OR 4.74; 95% CI 2.49-9.03, p<0.001, respectively) genotype of the COX-2 with an increased risk of chronic rhinosinusitis with nasal polyps.
Global gene expression profiling of APM treated HBE activated genes related to xenobiotic metabolism (CYP 1B1), endogenous ROS generation and response genes (DUOX1, SOD2, PTGS2) and pro-inflammatory responses associated with asthma or COPD such as IL-1α, IL-1β, IL-8, and CCL20.
To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA).
Clinical data show that mixed COX-1/COX-2 inhibitors such as aspirin, but not COX-2 selective inhibitors such as rofecoxib, induce bronchoconstriction and asthma in sensitive individuals.
These studies identified novel gene targets, such as CD40, DCNP1 and PTGS2, for asthma and allergen sensitization whereas many others replicated the genetic associations on known candidate genes for asthma and atopic dermatitis.
Clinical data show that mixed COX-1/COX-2 inhibitors such as aspirin, but not COX-2 selective inhibitors such as rofecoxib, induce bronchoconstriction and asthma in sensitive individuals.
To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA).
Our aim was to investigate the expression of COX-1 and COX-2 mRNA in primary human bronchial epithelial cells (HBEC) isolated from asthmatics and non-asthmatics.
Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls).
Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls).
A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway.
We identified five single nucleotide polymorphisms on three genes previously associated with asthma [interleukin (IL)-4RA, IL-13, ADAM33] and one gene associated with inflammation (cyclooxygenase-2).
Although the -765G>C polymorphism may have lower promoter activity and result in decreased COX-2 expression, it is not associated with asthma, disease severity, AIA or atopy in this Australian population.