Abstract
Monocytes are a distinct subset of myeloid cells with diverse functions in early inflammatory immune modulation. While previous studies have surveyed the role of miRNA regulation on different myeloid cell lines and primary cultures, the time-dependent kinetics of inflammatory stimulation on miRNA expression and the relationship between miRNA-to-target RNA expression have not been comprehensively profiled in monocytes. In this study, we use next-generation sequencing and RT-PCR assays to analyze the non-coding small RNA transcriptome of unstimulated and lipopolysaccharide (LPS)-stimulated monocytes at 6 and 24 hours. We identified a miRNA signature consisting of five mature miRNAs (hsa-mir-146a, hsa-mir-155, hsa-mir-9, hsa-mir-147b, and hsa-mir-193a) upregulated by LPS-stimulated monocytes after 6 hours and found that most miRNAs were also upregulated after 24 hours of stimulation. Only one miRNA gene was down-regulated and no other small RNAs were found dysregulated in monocytes after LPS treatment. In addition, novel tRNA-derived fragments were also discovered in monocytes although none showed significant changes upon LPS stimulation. Interrogation of validated miRNA targets by transcriptomic analysis revealed that absolute expression of most miRNA targets implicating in innate immune response decreased over time in LPS-stimulated monocytes although their expression patterns along the treatment were heterogeneous. Our findings reveal a potential role by which selective miRNA upregulation and stable expression of other small RNAs enable monocytes to develop finely tuned cellular responses during acute inflammation.
Highlights
Monocytes belong to a subset of circulating white blood cells that can further differentiate into macrophages and dendritic cells in solid tissues surrounding sites of injury [1]
Deep sequencing for small RNAs was performed by constructing 18-30-bp cDNA libraries from human monocyte RNA samples that were collected from seven different healthy donors
While we did not detect significant differential expression in any of the small RNA species after LPS stimulation (S7 and S8 Figs), we investigated whether any tRNA-derived fragment RNAs were conserved in human monocytes. tRFs are derived from transfer RNAs, and several species have been cloned and identified in few organisms and cell types [16, 17]
Summary
Monocytes belong to a subset of circulating white blood cells that can further differentiate into macrophages and dendritic cells in solid tissues surrounding sites of injury [1]. In vivo and in vitro studies have shown that monocytes and their derivatives function as an essential component of the innate immune system that mediate the host defense, serve as the first line of resistance to microbial attack, modulate tumor-associated immune defense responses, and regulate. Limited differential expression of small RNAs in LPS-treated monocytes. All of the authors except Wen-Yu Chou owned Amgen shares when the experiments were carried out. These do not alter the authors’ adherence to all the journal policies on sharing data and material
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