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

Siyu Yan; Runqiu Liu; Manyun Mao; Zhaoqian Liu; Wei Zhang; Yi Zhang; Jie Li; Cong Peng; Xiang Chen

doi:10.7717/peerj.7404

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

PeerJ. 2019 Aug 21:7:e7404. doi: 10.7717/peerj.7404. eCollection 2019.

Authors

Siyu Yan^{1

2

3}, Runqiu Liu^{1

2

3}, Manyun Mao^{1

2

3}, Zhaoqian Liu⁴, Wei Zhang⁴, Yi Zhang⁵, Jie Li^{1

2

3}, Cong Peng^{1

2

3}, Xiang Chen^{1

2

3}

Affiliations

¹ Department of Dermatology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
² Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital of Central South University, Changsha, Hunan, China.
³ Hunan Key Laboratory of Skin cancer and Psoriasis, Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁴ Institute of Clinical Pharmacology, Xiangya Hospital, Changsha, China.
⁵ JIUZHITANG Medicine Commerce CO, LTD, Changsha, China.

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 β-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-κB) 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 β-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-κB pathway and may have value in the treatment of CSU.

Keywords: BCG-PSN; Chronic spontaneous urticaria; Combined therapeutic effect; Mast cell.

Grants and funding

This study was funded by grants from the National Natural Science Foundations of China (grant No. 81430075 and 81225013 to Xiang Chen; grant No. 81673065 to Jie Li) and the National Key Research (grant No. 2016YFC095000 to Wei Zhang); the natural Science Foundation of Hunan Province (grant No.2016JJ3170 to Jie Li) and the Key Technology Research and Development Program of Hunan Province (grant No.2017SK2041 to Xiang Chen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.