Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

Abstract

Background/Aims: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. Methods: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. Results: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. Conclusions: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.

Proteomic analysis of exosome-like vesicles from Fasciola gigantica adult worm provides support for new vaccine targets against fascioliasis

“…The ESPs released by F. gigantica can directly regulate the differentiation of macrophages, dendritic cells (DCs) and T cells, and they have a modulating effect on DCs, thereby promoting downstream Th2/Treg responses [ 5 , 6 ]. Fasciola gigantica ESPs also induce macrophages toward an alternatively activated macrophage (M2 cells) phenotype, which promotes Th2/Treg responses [ 7 , 8 ].…”

Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica

“…Therefore, the possibility of that endotoxin derived from F. gigantica can not be excluded. Considering there might be parasite-derived endotoxin which should be counted an inherent component of ESPs, we did not conduct the endotoxin removal, as the same way of some similar studies [34,81]. The involvement of endotoxin with parasite ESPs in regulating host biological and immunological functions should not be ignored, especially during the serious parasite infection [82].…”

Macrophages as a Target for Treating Diabetic Foot Ulcers

“…Moreover, miR-33 was shown to favor M2 macrophage polarization through suppressing NLRP3 [111], a key inducer of IL-1β and inflammation [76,77]. Similarly, long noncoding RNAs (lncRNAs) have an emerging role in regulating macrophage polarization [112][113][114][115][116]. Besides miRNAs, long non-coding RNAs also play essential roles in macrophage phenotypic determination and control of inflammation [117].…”