Biochemical and Biophysical Research Communications
miR-181a and inflammation: miRNA homeostasis response to inflammatory stimuli in vivo
Highlights
► The increase of miR-181a is a homeostatic response to inflammatory stimuli. ► The increase of miR-181a is mediated by TLR-4 pathway activation. ► miR-181a serves as a novel marker for inflammatory diseases.
Introduction
Inflammatory stimuli cause tissue injures and are always associated with homeostatic responses. Inflammations are usually resolved in a timely manner, resulting in the elimination of inflammatory cells and release of inflammatory factors from the injured tissue. Inflammatory responses have an important function in protecting the body from deleterious consequences. Several endogenous factors against inflammatory responses have been produced at various stages and distinct locations [1]. However, the detailed mechanism of these endogenous factors remains unclear.
MicroRNAs (miRNAs) are key players in regulating inflammatory response. Some miRNAs have anti-inflammatory functions and serve as negative-feedback regulator of inflammation. Inflammatory stimuli, such as toll-like receptor, interleukin (IL)-1β, or IL-13, can stimulate the up-regulation of miR-147, miR-146a, or miR-21, respectively. These miRNAs either reduce inflammatory factor expression or suppress inflammatory response [2], [3], [4]. miR-203 is up-regulated in lesional psoriatic skin, which can directly regulate the expression of pro-inflammatory cytokines in keratinocytes [5]. Pro-inflammatory stimuli reduce miR-181b expression, and miR-181b suppresses nuclear factor-kappaB (NF-κB)-mediated vascular inflammation by targeting importin-α3 [6]. miR-181a suppresses oxidized low-density lipoprotein-stimulated immune inflammatory responses in dendritic cells by targeting c-Fos [7]. miR-181a/b directly targets the down-regulation of p300/CBP-associated factor, a coactivator of tumor necrosis factor alpha (TNF-α), which provides negative-feedback regulation to inflammatory reactions in liver epithelial cells [8]. However, some miRNAs serve as positive regulator of inflammation. miR-19b exacerbates inflammatory activation by targeting NF-κB signaling [9]. miR-125a/b constitutively activates the NF-κB pathway by targeting TNF-α-induced protein 3, which can strength and prolong NF-κB activity [10]. Lipopolysaccharide (LPS)-stimulated miR-16 gene transcription promotes NF-κB-mediated transactivation of IL-8 by suppressing the silencing mediator for retinoid and thyroid hormone receptor [11]. In pancreatic cancer cells, miR-301a represses NF-κB-repressing factor to activate NF-κB, which in turn promotes miR-301a transcription [12].
A previous study has demonstrated that miR-181a has an anti-inflammatory effect in vitro. However, no direct evidence exists on whether miR-181a is involved in inflammation in vivo. Therefore, miR-181a changes in inflammatory diseases will be useful in understanding the exact role of miR-181a in vivo and will protect or deteriorate tissue injuries from inflammatory stimuli.
Section snippets
LPS-induced animal model
Four-week old male Balb/c mice [specific pathogen-free (SPF) grade, Certified No. SCXK (Yue) 2008-0002] were obtained from Guangdong Medical Animal Center (Guang Zhou, China). Animals were kept in an environmentally controlled breeding room (temperature: 20 °C ± 2 °C; humidity: 60% ± 5%; 12 h dark/light cycle). The animals were fed standard laboratory chow diets with water ad libitum and fasted from 9:00 am to 3:00 pm before the experiments. The study was performed in strict accordance with the
miR-181a expressed concurrently with inflammation factors in blood of LPS-induced mice
We used in vivo models of inflammation to examine the expression of miR-181a. Balb/c mice were injected with LPS to induce inflammatory response. The expression level of miR-181a in the blood was evaluated by qRT-PCR at different time points after LPS induction. The level of miR-181a in blood increased almost twofold at 2 and 4 h after LPS induction, as shown in Fig. 1A. The expression of miR-181a started to decrease at 6 h, but nonetheless 50% higher than the basal level. After 8 h of LPS
Discussion
Recent studies have demonstrated that miRNA are key players in regulating inflammatory responses. Previous studies have indicated that miR-181a has an anti-inflammatory effect in vitro. However, whether miR-181a is involved in inflammation in vivo remains unclear. In the current study, we used LPS- and STZ-induced mice models to monitor acute and chronic inflammatory states in vivo. We demonstrated that miR-181a is up-regulated in the blood and abdominal macrophages, concurrently with
Acknowledgments
This study was supported by the National Natural Science Foundation of China (81072680), the Guangdong Natural Science Foundation (10151805702000002), and the Specialized Research Fund for the Doctoral Program of Higher Education of China (20100002120017).
References (19)
- et al.
Regulation of pro-inflammatory cytokines TNFα and IL24 by microRNA-203 in primary keratinocytes
Cytokine
(2012) - et al.
MicroRNA-181a represses ox-LDL-stimulated inflammatory response in dendritic cell by targeting c-Fos
J. Lipid Res.
(2012) - et al.
An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma)
J. Biol. Chem.
(1995) - et al.
PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway
Cytokine
(2011) - et al.
Hanging in the balance. endogenous anti-inflammatory mechanisms in tissue repair and fibrosis
J. Pathol.
(2012) - et al.
MiR-147, a microRNA that is induced upon toll-like receptor stimulation, regulates murine macrophage inflammatory responses
Proc. Natl. Acad. Sci. USA
(2009) - et al.
MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response
PLoS One
(2012) - et al.
MicroRNA-21 inhibits toll-like receptor 2 agonist-induced lung inflammation in mice
Exp. Lung Res.
(2011) - et al.
MicroRNA-181b regulates NF-κB-mediated vascular inflammation
J. Clin. Invest.
(2012)
Cited by (78)
Different expression profiles of circulating miR-31 and miR-181a in CD4<sup>+</sup> T cells and plasma of patients with oral lichen planus
2023, International ImmunopharmacologyEpigenetic reprogramming mechanisms of immunity during influenza A virus infection
2021, Microbes and InfectionBone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling
2020, Cellular SignallingCitation Excerpt :Interestingly, an increased expression of miR-181a-5p was found in BMSCs [14,15], and it was involved in the regulation of proliferation and immunosuppressive properties of MSCs by inhibiting TGF-β signaling [16]. Previous study has also illustrated that miR-181a-5p exerts an anti-inflammatory effect in vivo, thus protecting tissues from excessive injury [17]. However, the regulatory mechanism of miR-181a-5p-mediated compensation of inflammatory stimuli in SAP remains to be fully elucidated.
Aging Science Talks: The role of miR-181a in age-related loss of muscle mass and function
2020, Translational Medicine of AgingAltered expression of miR-181 affects cell fate and targets drug resistance-related mechanisms
2019, Molecular Aspects of MedicineCitation Excerpt :miR-181a mimics also significantly inhibites the levels of inflammatory factors (IL1b, IL6, and TNFα) (Xie et al., 2013a). The overexpression of miR-181a can be connected with a homeostatic reaction to inflammatory stimuli by activation of TLR4 pathway in macrophages (Xie et al., 2013b) and fibroblasts (Galicia et al., 2014). Moreover, a downregulation of miR-181a in parallel with the overexpression of IFN-γ, released by activated CD4 lymphocytes, was observed (Fayyad-Kazan et al., 2014).
EXPRESSION PATTERNS OF MATERNAL AND FETAL TISSUE AND EXOSOMAL MICRORNAS DURING PRE-INDUCTION OF LABOR (PILOT STUDY)
2024, Akusherstvo i Ginekologiya (Russian Federation)