scholarly journals Effect of the Fexofenadine on the expression of HRH-1 and HRH-4 receptor in Peripheral Blood Mononuclear Cell isolated from children with diagnosed allergy – in vitro study Short communication

2019 ◽  
Vol 22 ◽  
pp. 93-97
Author(s):  
Natalia Kordulewska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
Beata Jarmołowska ◽  
Elżbieta Kostyra

Purpose: Fexofenadine (FXF) is the active metabolite of terfenadine with selective peripheral H1 receptor antagonist activity. FXF is a third-generation antihistamine, non-sedating, rapid and very long acting used in symptoms associated with allergic diseases such as allergic rhinitis, asthma and dermatitis. The pleiotropic effects of histamine are mediated by four types of receptors that belong to the G-protein-coupled receptor family: histamine H1 receptor (HRH-1), histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Our hypothesis is that HRH-4 opens new possibility in treatment in allergy diseases and FXF could be the antagonist of both HRH-1 and HRH-4. Methods: We isolated a peripheral blood mononuclear cell (PBMC) from children with diagnosed allergies and healthy – control group and measured the HRH-1 and HRH-4 mRNA gene expression using Quantitive Real-Time PCR. We obtained the results from basal gene expression and after FXF and histamine stimulation. Results: HRH-1 mRNA basal gene expression shows significantly higher, and HRH-4 shows significantly lower expression in allergy group compared to control. In both groups HRH-1 mRNA gene expression was observed as statistically significant increased after histamine stimulation compared to cells not treated, while in HRH-4 only in allergy group we observed statistical increase. FXF successively blocked histamine affinity in HRH-1 mRNA gene expression but not in HRH-4, where we not observed any reaction. Conclusions: Results clearly overturned our hypothesis about the possibility of using FXF to block over-expression HRH-4 and open new way of treatment in allergy diseases.

2018 ◽  
Vol 27 (7) ◽  
pp. 2479-2486 ◽  
Author(s):  
Barbara Bonaparte Ribas de Alcântara ◽  
Felipe Melo Cruz ◽  
Fernando Luiz Affonso Fonseca ◽  
Beatriz da Costa Aguiar Alves ◽  
Matheus Moreira Perez ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Martin Cadeiras ◽  
Manuel P von Bayern ◽  
Anshu Sinha ◽  
Wei-Keat Lim ◽  
Teresa Palomero ◽  
...  

Background: Reconstruction of intracellular networks underlying complex processes is a formidable challenge. We hypothesized that the human peripheral blood mononuclear cell (PBMC) molecular network can be delineated using a systems-biological/computer-driven approach. Method: We used a large PBMC microarray library, an information-theoretic, reverse-engineering algorithm (ARACNe, Algorithm for the Reconstruction of Accurate Cellular Networks) and Chromatin Immunoprecipitation (ChIP) assay to reconstruct and validate a putative gene interaction network. Results: Gene expression data from 285 focused-microarrays obtained from 98 heart transplant patients enrolled in the Cardiac Allograft Rejection Gene expression Observational (CARGO) study was analyzed by ARACNe to identify highly connected “hub” genes. Biological criteria identified Transcription Factor CREB and its subnetwork as important candidates involved in the regulation of the alloimmune response. ARACNe predicted 29 putative direct interactions (first neighbor genes) of CREB (Fig. 1A ). Eleven of these (Fig. 1A red nodes) were previously reported (p<0.001) and 18 were not (Fig 1A , pink nodes). Out of the non validated, 14 suitable primers were identified and 11 could be immunoprecipitated (Fig 1B ), demonstrating binding of CREB to their promoter in vivo. Overall, 22 (75%) inferred CREB targets were validated; a significantly higher fraction than randomly expected (p<0.001, Fisher’s exact). Conclusion Our results confirm the accuracy of ARACNe to reconstruct the PBMC transcriptional network. Systems biological approaches may be used to identify immunomodulatory pharmacological targets. Figure 1


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