Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Abstract

Edited by George M. Carman Long non-coding RNAs (lncRNAs) have emerged as potential key regulators of the inflammatory response, particularly by modulating the transcriptional control of inflammatory genes. lncRNAs may act as an enhancer or suppressor to inflammatory transcription, function as scaffold molecules through interactions with RNA-binding proteins in chromatin remodeling complexes, and modulate dynamic and epigenetic control of inflammatory transcription in a gene-specific and time-dependent fashion. Here, we will review recent literature regarding the role of lncRNAs in transcriptional control of inflammatory responses. Better understanding of lncRNA regulation of inflammation will provide novel targets for the development of new therapeutic strategies.Because of the potentially destructive nature of the inflammatory response, the expression of inflammation-related genes is finely regulated at multiple levels, including transcription, mRNA processing, translation, phosphorylation, and degradation. Transcription represents an essential, and often the most important, regulatory determinant of the inflammation process. Many signaling pathways and transcription factors are involved in the inflammatory response, including the transcription factor nuclear factor-B (NF-B), 2 MAPK, and JAK/ STAT pathways, together controlling a multitude of inflammatory response genes (1, 2). Upon activation, these pathways directly activate and induce the expression of a limited set of transcription factors that promote the transcription of inflammatory genes. Whereas the mechanisms of initial activation and subsequent nuclear translocation of associated transcription factors for these signaling pathways are well-characterized, how the transcription of inflammatory genes is finely controlled in the nucleus to ensure that each individual gene is transcribed at the "right" place at the "right" time remains elusive. Perhaps this can be best represented by the inflammatory transcription induced by NF-B. The NF-B signaling cascade can be activated by inflammatory signals, including LPS, TNF-␣, IL-1␤, and reactive oxygen species, among others; many Toll-like receptors (TLRs) also activate NF-B (3-8).Prior to an activating signal, NF-B dimers are sequestered in the cytoplasm and held inactive by association with I B proteins (9). Activating stimuli cause I B degradation (10, 11), and consequently, free NF-B dimers translocate to the nucleus, bind to B sites, and promote gene transcription (12). Common targets of NF-B include inflammatory cytokines, chemokines, adhesion molecules, cytoprotective proteins, and proteins regulating cell differentiation, proliferation, and survival (13,14). In addition to its initial cytoplasmic activation, both the recruitment of NF-B to target genes in the nuclei and NF-B-induced transcriptional events after recruitment are finely controlled events to ensure proper transactivation of NF-B target genes (15). Indeed, several waves of gene transcription have been demonstrated in macrophages following LP...

The correlation of long non‐coding RNA intersectin 1‐2 with disease risk, disease severity, inflammation, and prognosis of acute ischemic stroke

“…From pathological perspective of AIS, inflammation serves as a critical part in the disease exacerbation, which not only directly affects inflammatory pathways (including nuclear factor kappa‐light‐chain‐enhancer of activated B cell (NF‐κB) and Toll‐like receptor (TLR) pathways) to damage vascular wall, then changes vascular structure and promotes atherosclerosis, thereby decreasing blood flowing and increasing risk of AIS, but also indirectly increases neurocyte death through inducing TNF‐dependent apoptosis or necrosis in ischemic conditions, thereby accelerating the tissue damage in relevant part of the brain, retina, or spinal cord and facilitating the progression of AIS . According to the previous studies, several lncRNAs act as enhancers of inflammatory responses in AIS by activating inflammation‐related pathways such as NF‐κB pathway, TRL pathway, and JAK/STAT pathway . For instance, increased lncRNA H19 expression is associated with impaired neurological function and increased TNF‐α level in AIS animal models .…”

“…In the present study, we discovered that (a) lnc-ITSN1-2 was highly and JAK/STAT pathway. [19][20][21][22] For instance, increased lncRNA H19 expression is associated with impaired neurological function and increased TNF-α level in AIS animal models. 23 Antisense non-coding RNA in the cyclin-dependent kinase inhibitor 4 locus (ANRIL), an antisense lncRNA co-clustered with p15/CDKN2B-p16/CDKN2A-p14/ ARF, is overexpressed in cerebral infarction rat models and plays a pro-inflammatory role by activating NF-κB pathway.…”

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

“…LncRNAs are ncRNAs with critical biological roles and a length of more than 200 nucleotides . The mechanisms of lncRNAs remain unclear, but increasing number of in vitro and in vivo studies have shown that lncRNAs can be expressed in macrophage during its development and control some gene expression . However, a systematic review uncovered the interactions among lncRNAs expressed in macrophage is not available.…”

Thematic Minireview Series: Inflammatory transcription confronts homeostatic disruptions

“…E-mail: nbazan@lsuhsc.edu. 2 The abbreviations used are: lncRNA, long non-coding RNA; lincRNA, long intergenic non-coding RNA; AhR, aryl hydrocarbon receptor; DHA, docosahexaenoic acid.…”

“…Mathy and Chen (2) refer to the evolving role of long noncoding RNAs (lncRNAs) 2 as transcriptional regulators of the inflammatory response. A group of lncRNAs is induced as part of the response to inflammation and acts as an enhancer or a suppressor of inflammatory transcription, with members behaving as scaffolds with RNA-binding proteins in chromatinremodeling complexes.…”