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Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

ABSTRACT: Background:Chronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Dysfunction of immune cells, such as T cells, mast cells, and basophils, is involved. Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN), an immunomodulator partially extracted from BCG, can be used in the combined treatment of CSU with an unknown mechanism. Methods:To study the therapeutic effect and mechanism of BCG-PSN on CSU, we initially assessed the clinical efficacy in 110 enrolled CSU patients of 4-week antihistamine monotherapy vs. antihistamine plus BCG-PSN combined therapy. Subsequently, to explore the further mechanism of BCG-PSN, the mast cell line RBL-2H3 pretreated with BCG-PSN was used to evaluate the transcriptional expression profiles via lncRNA sequencing. Real time PCR was conducted to validate the candidate gene expression. Results:We found no significant difference in treatment efficacy between the BCG-PSN group (71.7%) and the monotherapy group (71.9%). However, the average time of complete relief in the BCG-PSN group was significantly shorter than that in the monotherapy group (36.77 ± 17.33 vs. 51.27 ± 16.80, p = 0.026). In vitro experiments showed that BCG-PSN inhibited ?-hexosaminidase release rates in IgE-sensitized RBL-2H3 cells (p < 0.001). Sequencing data revealed the expression profiles of functional genes, including a significant decrease in Erb-B2 receptor tyrosine kinase 4, which can be regulated by the nuclear factor kappa B (NF-?B) pathway. Discussion:CSU is a chronic, recurrent disease with complex pathogenesis. Mast cells and basophils are the primary target cells of the disease. BCG-PSN decrease the ?-HEX release rates and regulated IgE-mediated mast cell activation in RBL-2H3 cells by mediating immune-related gene expression including ERBB4. These findings suggest that BCG-PSN may mediate ERBB4 expression via the NF-?B pathway and may have value in the treatment of CSU.

SUBMITTER: Yan S

PROVIDER: S-EPMC6708377 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

Yan Siyu S Liu Runqiu R Mao Manyun M Liu Zhaoqian Z Zhang Wei W Zhang Yi Y Li Jie J Peng Cong C Chen Xiang X

PeerJ 20190821

<h4>Background</h4>Chronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Dysfunction of immune cells, such as T cells, mast cells, and basophils, is involved. Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN), an immunomodulator partially extracted from BCG, can be used in the combined treatment of CSU with an unknown mechanism.<h4>Methods</h4>To study the therapeutic effect and mechanism of BCG-PSN on CSU, we initially a ...[more]

PMID: 31497384

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Project description:BackgroundThis study aimed to explore the mechanism of Bacillus Calmette-Guerin polysaccharide and nucleic acid injection (BCG-PSN) targeting the transient receptor potential vanilloid subtype 1 (TRPV1) pathway for atopic dermatitis (AD) in mice.MethodsExperiment 1: a total of 30 Kunming (KM) mice were randomized into blank control, model, BCG-PSN low-dose (25 g/kg), BCG-PSN medium-dose (75 g/kg), BCG-PSN high-dose (225 g/kg), and positive drug (hydrocortisone 25 mg/kg) control groups. The AD model mice were established by induction with 2,4-Dinitrochlorobenzene (DNCB). After treatment in groups, the symptom score and scratching frequency in skin lesions were observed. The levels of immunoglobulin E (IgE), interleukin (IL)-4, IL-31, and IL-13 in serum were detected, as well as the levels of tumor necrosis factor-α (TNF-α), TRPV1, and nuclear factor (NF)-κB p65 in skin lesions in each group. Experiment 2: the optimal dose of BCG-PSN in Experiment 1 was adopted. A total of 20 KM mice were randomized into blank control, model, BCG-PSN, and BCG-PSN + PAC (PAC-14028) groups. The symptom score and scratching frequency in skin lesions were observed. The levels of IgE, IL-4, IL-31, and IL-13 in serum were detected, as well as the levels of TNF-α and TRPV1 in skin lesions in each group.ResultsIn Experiment 1, compared with the blank control group, the ear tissues of mice in model groups developed AD, with increased symptom score, scratching frequency, levels of IgE, IL-4, IL-31, and IL-13 in serum and levels of TNF-α, TRPV1, and NF-κB p65 in skin lesions. Compared with the model group, BCG-PSN low-dose, BCG-PSN medium-dose, BCG-PSN high-dose, and positive drug control groups had reduced AD symptoms, decreased symptom score, and decreased scratching frequency, with declined expression of each inflammatory substance, including the greatest decrease in the medium-dose group. In Experiment 2, after BCG-PSN was combined with PAC, the inflammation indexes decreased compared with those in the model group, and increased compared with those in the BCG-PSN group.ConclusionsIntramuscular BCG-PSN can target the TRPV1 pathway, inhibit inflammation, and improve the symptoms of AD mice.

Project description:BackgroundThe Bacillus Calmette-Guerin (BCG) vaccine has been in use for 99 years, and is regarded as one of the oldest human vaccines known today. It is recommended primarily due to its effect in preventing the most severe forms of tuberculosis, including disseminated tuberculosis and meningeal tuberculosis in children; however, its efficacy in preventing pulmonary tuberculosis and TB reactivation in adults has been questioned. Several studies however have found that asides from its role in tuberculosis prevention, the BCG vaccine also has protective effects against a host of other viral infections in humans, an effect which has been termed: heterologous, non-specific or off-target.ObjectivesAs we approach 100 years since the discovery of the BCG vaccine, we review the evidence of the non-specific protection offered by the vaccine against viral infections, discuss the possible mechanisms of action of these effects, highlight the implications these effects could have on vaccinology and summarize the recent epidemiological correlation between the vaccine and the on-going COVID-19 pandemic.ResultsSeveral epidemiological studies have established that BCG does reduce all-cause mortality in infants, and also the time of vaccination influences this effect significantly. This effect has been attributed to the protective effect of the vaccine in preventing unrelated viral infections during the neonatal period. Some of such viral infections that have been investigated include: herpes simplex virus (HSV), human Papilloma virus (HPV), yellow fever virus (YFV), respiratory syncytial virus (RSV) and influenza virus type A (H1N1). These effects are thought to be mediated via induction of innate immune memory as well as heterologous lymphocytic activation. While epidemiological studies have suggested a correlation, the potential protection of the BCG vaccine against COVID-19 transmission and mortality rates is currently unclear. Ongoing clinical trials and further research may shed more light on the subject in the future.ConclusionBCG is a multifaceted vaccine, with many numerous potential applications to vaccination strategies being employed for current and future viral infections. There however is a need for further studies into the immunologic mechanisms behind these non-specific effects, for these potentials to become reality, as we usher in the beginning of the second century since the vaccine's discovery.

Dataset Information

Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

Publications

Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

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