Retracted: Effects of RNA interference–mediated E‐selectin gene silencing on cell adhesion molecule expression and cell‐cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria

Abstract

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion molecule expression and on cell-cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme-linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL-4), interferon-γ (IFN-γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA- SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse-transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL-4, IFN-γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1, CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

“…It is reported that SELE is significantly upregulated in skin lesions in urticaria and may be involved in the pathogenesis of urticaria [32]. Meng et al [33] constructed a contact urticaria mouse model by inducing anti-dinitrophenol immunoglobulin E combined with 2,4-dinitrofluorobenzene. Next, the deletion of SELE by siRNA showed that E-selectin, intercellular cell adhesion molecule-1, CD62L, and eosinophil cationic protein expressions in the mouse skin significantly decreased compared with the initial levels and the adhesion of leukocytes receded, indicating that inhibiting SELE expression can reduce the adhesion of leukocytes and greatly weaken the inflammatory response in CSU, thus may act as a biomarker in CSU treatment [33].…”

“…Meng et al [33] constructed a contact urticaria mouse model by inducing anti-dinitrophenol immunoglobulin E combined with 2,4-dinitrofluorobenzene. Next, the deletion of SELE by siRNA showed that E-selectin, intercellular cell adhesion molecule-1, CD62L, and eosinophil cationic protein expressions in the mouse skin significantly decreased compared with the initial levels and the adhesion of leukocytes receded, indicating that inhibiting SELE expression can reduce the adhesion of leukocytes and greatly weaken the inflammatory response in CSU, thus may act as a biomarker in CSU treatment [33]. CCL17/miR-125a-5p CCL17 is a chemokine tracking Th2 cells and involved in a variety of Th2-mediated inflammatory diseases, including atopic dermatitis [34].…”

SELE Downregulation Suppresses Mast Cell Accumulation to Protect against Inflammatory Response in Chronic Idiopathic Urticaria

“…A previous study revealed that significantly decreased SELE serum levels may reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin [27]. SELE silencing has been shown to potentially inhibit the development of immunologic contact urticaria by inhibiting the cell adhesion ability of vascular endothelial cells [28]. In the present study, we detected that SELE silencing could prevent the production of TNF-α, HRF, IL-6, and histamine from mast cells and consequently ameliorate the progression of CIU.…”

“…The inhibited secretion of IL-6 and TNF-α from mast cells may contribute to the treatment of allergic inflammation [29]. A previous study highlighted elevated levels of histamine as well as an increased positive expression rate of SELE as indicators of the successful establishment of mouse models of immunologic contact urticaria [28], suggesting a positive correlation between histamine and SELE. Besides, an increased endothelial surface expression of SELE has been reported to exert a synergistic effect on histamine and TNF-α [30].…”