scholarly journals Glucocorticoid-induced Changes in the Transcriptional Activity of Genes of the Innate and Adaptive Immune System in the Blood of Patients with Acute Urticaria

2021 ◽  
Vol 9 (A) ◽  
pp. 1024-1030
Author(s):  
Alina Petruk ◽  
Iryna Kamyshna ◽  
Mariia Shkilna ◽  
Aleksandr Kamyshnyi

Background: A number of the main effects of glucocorticoids (GCs) are their direct action on T cells, mainly through the transcriptional regulation: elevated expression of immune-regulatory proteins, inhibitory receptors, and reduced expression of pro-inflammatory cytokines, co-stimulatory molecules, and cell cycle mediators. But controversies arise due to the clinical effectiveness of GCs in the treatment of acute urticaria. Methods: In our research, we applied a pathway-specific PCR array (Human Innate & Adaptive Immune Responses RT2 Profiler PCR Array, QIAGEN, Germany) to detect and verify innate & adaptive immune responses pathway-focused genes expression in the blood of patients with acute urticaria who received treatment with glucocorticoids in addition to standard therapy. Results: Adding glucocorticoids to standard therapy did not notably affect the nature of the clinical presentation of acute urticaria, which was assessed according to the UAS scale (urticaria activity score). Analysis of the transcriptional profile of peripheral blood mononuclear cells in patients with acute urticaria against the background of glucocorticoid therapy showed the induction expression of the FOXP3 and IL10 genes against the background of repression of the transcriptional activity of the genes for chemokines and cytokines CCL5, CXCL8, IFNG, IL2, IL5, IL17A, IL1B, and TNF. Glucocorticoid-induced changes in the transcriptome also manifested by pronounced repression in genes of CD40 and CD80 (B7-1) co-stimulatory molecules, transcriptional regulators of Th1-cells differentiation - TBX21 and STAT1, Th17 cells - RORC, NLRP3-inflammasome genes, and the transcription factor NFKB1 compared with the control group. Conclusions: Adding glucocorticoids to the standard therapy of acute urticaria has a pronounced immunosuppressive potential at the transcriptome level of immune response genes in the blood; however, it does not have any noticeable clinical effect.

2008 ◽  
Vol 82 (11) ◽  
pp. 5359-5367 ◽  
Author(s):  
Patricia Devaux ◽  
Gregory Hodge ◽  
Michael B. McChesney ◽  
Roberto Cattaneo

ABSTRACT Patients recruited in virus-based cancer clinical trials and immunocompromised individuals in need of vaccination would profit from viral strains with defined attenuation mechanisms. We generated measles virus (MV) strains defective for the expression of either the V protein, a modulator of the innate immune response, or the C protein, which has multiple functions. The virulence of these strains was compared with that of the parental wild-type MV in a natural host, Macaca mulatta. Skin rash, viremia, and the strength of the innate and adaptive immune responses were characterized in groups of six animals. Replication of V- or C-protein-defective viruses was short-lived and reached lower levels in peripheral blood mononuclear cells and lymphatic organs compared to the wild-type virus; none of the mutants reverted to the wild type. The neutralizing antibody titers and MV-specific T-cell responses were equivalent in monkeys infected with the viral strains tested, documenting strong adaptive immune responses. In contrast, the inflammatory response was better controlled by wild-type MV, as revealed by inhibition of interleukin-6 and tumor necrosis factor alpha transcription. The interferon response was also better controlled by the wild-type virus than by the defective viruses. Since V- and C-defective MVs induce strong adaptive immune responses while spreading less efficiently, they may be developed as vaccines for immunocompromised individuals. Moreover, MV unable to interact with single innate immunity proteins may be developed for preferential replication in tumors with specific contexts of vulnerability.


2020 ◽  
Vol 10 (2) ◽  
pp. 271-275
Author(s):  
Ying Li ◽  
Yongshan Tang

Sepsis is a common clinical disease. The NLRP3 inflammasome is a multiprotein complex that is involved in both innate and adaptive immune responses. However, the expression of NLRP3 in patients with sepsis has not been elucidated. 98 patients with sepsis before and after treatment were selected and 106 healthy volunteers were used as the control group. PBMCs were isolated from each group to measure NLRP3 and Caspase 1 level Real time PCR. The expression of serum procalcitonin (PCT), C-reactive protein (CRP), IL-1β and IL-18 was analyzed by ELISA. NLRP3 and Caspase 1 level was significantly increased in sepsis patients before treatment with increased secretion of IL-1β and IL-18 in serum and elevated level of PCT and CRP (P < 0.05). NLRP3, Caspase 1 expression, IL-1β and IL-18 secretion were positively correlated with serum PCT and CRP in patients with sepsis (P < 0.05). After treatment, NLRP3 and Caspase 1 mRNA expression was significantly decreased and serum IL-1β and IL-18 secretion was significantly decreased (P < 0.05). NLRP3 is increased in sepsis and IL-1β and IL-18 secretion is elevated, implying the involvement of NLRP3 in the occurrence and development of sepsis.


2019 ◽  
Vol 8 (6) ◽  
pp. 849 ◽  
Author(s):  
Óscar Brochado-Kith ◽  
Alicia Gómez Sanz ◽  
Luis Miguel Real ◽  
Javier Crespo García ◽  
Pablo Ryan Murúa ◽  
...  

Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).


Sign in / Sign up

Export Citation Format

Share Document