MiR-154-5p-MCP1 Axis Regulates Allergic Inflammation by Mediating Cellular Interactions

Abstract

In a previous study, we have demonstrated that p62, a selective receptor of autophagy, can regulate allergic inflammation. In the present study, microRNA array analysis showed that miR-154-5p was increased by antigen (DNP-HSA) in a p62-dependent manner in rat basophilic leukemia cells (RBL2H3). NF-kB directly increased the expression of miR-154-5p. miR-154-5p mediated in vivo allergic reactions, including passive cutaneous anaphylaxis and passive systemic anaphylaxis. Cytokine array analysis showed that antigen stimulation increased the expression of MCP1 in RBL2H3 cells in an miR-154-5p-dependent manner. Reactive oxygen species (ROS)-ERK-NF-kB signaling increased the expression of MCP1 in antigen-stimulated RBL2H3 cells. Recombinant MCP1 protein induced molecular features of allergic reactions both in vitro and in vivo. Anaphylaxis-promoted tumorigenic potential has been known to be accompanied by cellular interactions involving mast cells, and macrophages, and cancer cells. Our experiments employing culture medium, co-cultures, and recombinant MCP1 protein showed that miR-154 and MCP1 mediated these cellular interactions. MiR-154-5p and MCP1 were found to be present in exosomes of RBL2H3 cells. Exosomes from PSA-activated BALB/C mouse induced molecular features of passive cutaneous anaphylaxis in an miR-154-5p-dependent manner. Exosomes from antigen-stimulated RBL2H3 cells enhanced both tumorigenic and metastatic potentials of B16F1 melanoma cells in an miR-154-5p-dependent manner. Exosomes regulated both ROS level and ROS mediated cellular interactions during allergic inflammation. Our results indicate that the miR-154-5p-MCP1 axis might serve as a valuable target for the development of anti-allergy therapeutics.

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

“…In addition, they can act as transporters of different miRNAs, which exert their action on the target cell [226]. Precisely, two of them have been characterized in anaphylaxis, miR-135-5p and miR-154-5p, which can regulate allergic inflammation in a p62 protein-dependent manner [179,227].…”

A Data-Mining Approach to Identify NF-kB-Responsive microRNAs in Tissues Involved in Inflammatory Processes: Potential Relevance in Age-Related Diseases

“…Only three miRNAs, such as miR-154, miR-377, and miR-885-5p, were not retrieved in previous analysis [ 81 ]. However, based on recent literature, all of them are related to NF-kB/inflammation pathways [ 82 , 83 , 84 ]. All of the 68 NF-kB responsive miRNAs are therefore included in the Venn diagram reported in panel B, highlighting that these miRNAs identified as tissues expressed miRNAs are also detectable in blood, and most of them were identified inside extracellular vesicles, i.e., exosomes (miRNAs depicted in inner circles Figure 7 B).…”

miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury

“…It has been shown that miR-154-5p is able to reverse a circ-Scmh1-induced microglial polarisation from M1 to M2 via STAT6 binding [ 23 ], which may alter TLR7 signalling [ 46 ]. Also, miR-154-5p seems to be involved in allergic inflammation mediated by MCP-1 [ 47 ]. Although we determined some cytokines in addition to TNF at the mRNA level produced in response to miR-154-5p, an in-depth characterisation of the cytokine/chemokine pattern released from microglia responding to miR-154-5p would be valuable to fully understand the interaction between miR-154-5p and TLR7 as well as the cellular consequences of such an interaction, especially in human and disease contexts.…”

“…Although we determined some cytokines in addition to TNF at the mRNA level produced in response to miR-154-5p, an in-depth characterisation of the cytokine/chemokine pattern released from microglia responding to miR-154-5p would be valuable to fully understand the interaction between miR-154-5p and TLR7 as well as the cellular consequences of such an interaction, especially in human and disease contexts. Also, further research is required to characterise the role of miR-154-5p in inducing a microglial M1 and/or M2 state and to assess whether TLR signalling and further signalling cascades, such as MCP-1, which miR-154-5p is considered to regulate [ 47 ], are involved in these processes. Finally, the alteration of some signalling components, but not others such as MYD88 and TRIF, is of interest.…”