Figure - available from: Mediators of Inflammation
This content is subject to copyright. Terms and conditions apply.
Clinical and histopathological characterizations of rat eyes and tissues from normal and EAU individuals on day 12 postimmunization. Retinal images were captured with a handheld retinal camera, and hematoxylin and eosin staining was performed on eye sections. Bar = 50 μm.
Source publication
Uveitis is a serious eye disease that usually damages young adult’s health. MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate messenger RNA (mRNA) expression. It is predicted that rno-miR-30b-5p can regulate the expressions of interleukin-10 (IL-10) and Toll-like receptor 4 (TLR4). In this study, the regulatory role of rno-miR-3...
Citations
... In an animal model of endotoxin-induced uveitis (EIU), miR-93 was found to bind to IRAK4 in the NF-κB pathway, thereby inhibiting NF-κB activation and thus negatively regulating the generation of M1-type macrophage-related proinflammatory cytokines [79]. miR-30b-5p is downregulated in the spleen, lymph nodes, and eye tissues of rats with autoimmune uveitis, and both in vitro and in vitro experiments have confirmed that supplementation with miR-30b-5p can reduce the level of IL-10 and TLR4-positive cells, thereby having a certain inhibitory effect on uveitis [95]. Meanwhile, miR-155 has been shown to promote M1 macrophage polarization and thus exert proinflammatory effects, showing remission to EAU after reducing miR-155 expression levels [67,96]. ...
Macrophages are innate immune cells in the organism and can be found in almost tissues and organs. They are highly plastic and heterogeneous cells and can participate in the immune response, thereby playing a crucial role in maintaining the immune homeostasis of the body. It is well known that undifferentiated macrophages can polarize into classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages) under different microenvironmental conditions. The directions of macrophage polarization can be regulated by a series of factors, including interferon, lipopolysaccharide, interleukin, and noncoding RNAs. To elucidate the role of macrophages in various autoimmune diseases, we searched the literature on macrophages with the PubMed database. Search terms are as follows: macrophages, polarization, signaling pathways, noncoding RNA, inflammation, autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, lupus nephritis, Sjogren’s syndrome, Guillain-Barré syndrome, and multiple sclerosis. In the present study, we summarize the role of macrophage polarization in common autoimmune diseases. In addition, we also summarize the features and recent advances with a particular focus on the immunotherapeutic potential of macrophage polarization in autoimmune diseases and the potentially effective therapeutic targets.
... miR-146a was found to be upregulated in EAU retina; moreover, its overexpression was closely associated with the inflammation score of EAU by regulating IL-1β/MCP-1 and IL-10 and IL-17 (Watanabe et al., 2016). In EAU, miR-30b-5p was reported to be involved in disease development by targeting IL-10 and TLR4 in T cells (Sun et al., 2018). It was well demonstrated that miR-142-5p could control Tregs' suppressive function by regulating intracellular cAMP (Talebi , and miR-21 could promote Th17 differentiation by regulating TGF-β signaling. ...
... A study by YY Sun reported that downregulated miR-30b-5p could regulate the levels of IL-10-and TLR4-positive cells (Sun et al., 2018;Torri et al., 2017). Collectively, these observations indicate that miRNAs are vital regulators of EAU development by regulating the Treg/Th17 balance. ...
Th17 and regulatory T cells (Tregs) play crucial roles in the pathogenesis of autoimmune diseases. Th17/Treg homeostasis is critically involved in maintaining the immune balance. Disturbed Th17/Treg homeostasis contributes to the progression of autoimmune diseases. MicroRNAs (miRNAs) have emerged as a new vital factor in the regulation of disturbed Th17/Treg homeostasis. To better understand the epigenetic mechanisms of miRNAs in regulating Treg/Th17 homeostasis, we included and evaluated 97 articles about autoimmune diseases and found that miRNAs were involved in the regulation of Treg/Th17 homeostasis from several aspects positively or negatively, including Treg differentiation and development, Treg induction, Treg stability, Th17 differentiation, and Treg function. Uveitis is one of the ocular autoimmune diseases, which is also characterized with Th17/Treg imbalance. However, our understanding of the miRNAs in the pathogenesis of uveitis is elusive and not well-studied. In this review, we further summarized miRNAs found to be involved in autoimmune uveitis and their potential role in the regulation of Th17/Treg homeostasis.
... Among them, the expression of miR-223 and miR-146a was consistent with the increase in IL-1β/ McP-1 in the eye with EAU (Watanabe et al., 2016). Furthermore, Sun et al. demonstrated that rno-miR-30b-5P expression was decreased in the spleen, lymph nodes and eye tissues of EAU rats, and rno-miR-30b-5P played a role in the pathogenesis of uveitis by directly regulating the levels of IL-10-and TLR4-positive cells to affect the development of uveitis (Sun et al., 2018). Th17 cells play a key role in the pathogenesis of autoimmune uveitis (Peng et al., 2007). ...
... Furthermore, Zhang et al. demonstrated that miR-182-5p mimicry inhibited the pathogenic Th17 response in EAU mice by directly inhibiting the transcription promoter TATA-binding protein-related factor 15 (Zhang et al., 2020b). In addition, Sun et al. revealed that rno-miR-30b-5p mimics play a role in the pathogenesis of uveitis by reducing the number of IL-10-and TLR4-positive cells and influencing the development of uveitis (Sun et al., 2018). However, research on miRNAs for the treatment of autoimmune uveitis is in its early stages and requires broader investigations. ...
Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt–Koyanagi–Harada (VKH) disease and Behcet’s disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.
... The miRNA-30 family includes miR-30b and miR-30d, together with miR-30a, miR-30c, and miR-30e. miR-30b could regulate interleukin-10 and toll-like receptor 4 expressions in T-lymphocytes [48], may participate in NLRP3 inflammasome expression in chronic liver injury [49] and be involved in the inflammatory response of acute lung injury in children [50]. Meanwhile, miR-30d modulates the survival programs of neural cells by regulating autophagy and apoptosis [51]. ...
Several researchers have testified that feeding with diets high in rice grain induces subacute ruminal acidosis and increases the risk of gastrointestinal inflammation. However, whether diets high in rice grain affect spleen growth and related molecular events remains unknown. Therefore, the present study was conducted to investigate the effects of feeding a high-concentrate (HC) diet based on rice on the growth and microRNA expression profiles in goat spleen. Sixteen Liuyang black goats were used as an artiodactyl model and fed an HC diet for five weeks. Visceral organ weight, LPS (lipopolysaccharide) concentration in the liver and spleen, and microRNA expression were analyzed. The results showed that feeding an HC diet increased the heart and spleen indexes and decreased the liver LPS concentration (p < 0.05). In total, 596 microRNAs were identified, and twenty-one of them were differentially expressed in the spleens of goats fed with the HC diet. Specifically, several microRNAs (miR-107, miR-512, miR-51b, miR-191, miR-296, miR-326, miR-6123 and miR-433) were upregulated. Meanwhile, miR-30b, miR-30d, miR-1468, miR-502a, miR-145, miR-139, miR-2284f, miR-101 and miR-92a were downregulated. Additionally, their target gene CPPED1, CDK6, CCNT1 and CASP7 expressions were inhibited (p < 0.05). These results indicated that the HC diet promoted the growth of the heart and spleen. The HC diet also regulated the expression of miR-326, miR-512-3p, miR-30b, miR-30d, miR-502a and their target genes (CPPED1, CDK6 and CCNT1) related to the enhancement of splenocyte proliferation. The HC diet also modulated the expression of miR-15b-5p, miR-1468 and miR-92a, related to the suppression of splenocyte apoptosis.
... Toll-like receptor 4(TLR-4) is the primary signal cell receptor recognized and activated by lipopolysaccharide. TLR-4 plays a key role in the onset of uveitis and eventually leads to the activation of inflammatory cytokines and inflammation pathological reactions [71]. Li et al. [72] found that TLR4 signaling pathway may involve in the pathogenesis of acute anterior uveitis. ...
Background:
As the spectrum of ophthalmic diseases keeps changing, uveitis has gradually become one of the major blinding eye diseases in the world. In recent years, it has become a research hotspot to select effective components for uveitis treatment from natural drugs.
Methods:
We searched PubMed and EMBASE databases for studies written in English as well as Chinese National Knowledge Infrastructure (CNKI), CQVIP, and Wan Fang database for studies written in Chinese (inception through 30 December 2020).
Results:
Eight kinds of natural product ingredients were included in this article. They were found to not only regulate the expression of cytokines, proliferation, and differentiation of T help cells but also inhibit the damage of cytokines and inflammatory cells to uvea, blood aqueous barrier, and blood retinal barrier.
Conclusion:
Natural product ingredients have their unique advantages in the treatment of uveitis. They have good anti-inflammatory effects without causing serious adverse reactions, which enables them to be promising choices for preventive and therapeutic strategy of uveitis.
... The expression of IL-10 and TLR4 genes and proteins can be decreased by rno-miRNA-30b-5p mimics, therefore influencing the pathogenesis of uveitis. Thus, rno-miRNA-30b-5p may be a new therapeutic target for uveitis [82]. Researches have also shown that miRNA-410 is a major regulator of SLE pathogenesis by targeting STAT3 to control IL-10 expression [83]. ...
Breast Cancer (BC) is the most common cancer in women and the second cause of death in females due to cancers. Most genetic studies point to a significant relationship between Interleukin 10 (IL-10) and BC. IL-10 is strongly expressed in tissues of BC and negatively correlated with the prognosis of several tumors, including breast cancer. In breast cancer cells, the down-regulation of miRNA-141 inhibits IL-10 and contributes to an up-regulation of COX-2, PGE-2, and TNF-α expression. Long non-coding RNR SNHG1 has been increased in CD4 + TIL cells in patients with breast cancer, whereas siRNA-SNHG1 can decrease the expression of Foxp3 and IL-10. Overexpression of IL-10 failed to manage immunogenic cancer. And the inhibition of IL-10Rα improved the therapeutic benefit of chemotherapy in the breast cancer model. The mechanisms of IL-10 in breast cancer are controversial. Interleukin-10 is documented to demonstrate both anti-and pro-tumor acts. IL-10 is strongly expressed in tissues of BC, which has a negative correlation with breast cancer prognosis and tumor marker. Besides, IL10 levels in serum are elevated for patients with BC than normal controls people, which also correlates with poorer outcomes. IL-10 stimulated cancer cell replication and metastasis. IL10 is currently under study as a potential therapeutic targeting inflammatory disease as well as cancer. In conclusion, IL-10 seems to be the future diagnostic biomarker and therapy target of breast cancer. Though lncRNA seems to be a significant research spot, very little research in lncRNA and IL-10 is found. Consequently, in future IL-10 research topics, new studies related to lncRNA could occur.
... Additionally, 36 upregulated miRNAs and 31 downregulated miRNAs were found in peripheral blood lymphocytes from rats with EAU (Guo et al., 2015), and targets of these differentially expressed miRNAs were implicated in some immune signaling pathways such as T-cell receptor signaling pathway and Toll-like receptor signaling pathway, both of which are closely associated with the pathogenesis of EAU (Horai et al., 2013;Xiao et al., 2016). More recently, it was shown that miR-30b-5p expression was decreased in spleen, lymph nodes, and eye tissues of EAU rats, and miR-30b-5p directly targeted IL-10 and TLR4 in T cells and reduced the level of IL-10 and TLR4 positive cells, regulating the development of EAU (Sun et al., 2018). ...
MicroRNAs (miRNAs) are evolutionarily conserved short non-coding RNAs that act at post-transcriptional regulation of gene expression by destroying target messenger RNA or inhibiting its translation. Recently, miRNAs have been identified as important regulators in autoimmunity. Aberrant expression and function of miRNAs can lead to dysfunction of immune system and mediate autoimmune disorders. Here, we summarize the roles of miRNAs that have been implicated in three representative ocular autoimmune disorders, including autoimmune uveitis, Grave’s ophthalmopathy, and Sjögren’s syndrome dry eye, and discuss the potential of miRNAs as biomarkers and therapeutic targets for the diagnosis and treatment of these diseases.
... rno-miRNA-30b-5p mimics can reduce the expression of IL-10 and TLR4 genes and proteins, thereby affecting the pathogenesis of uveitis. Therefore, rno-miRNA-30b-5p may be a new therapeutic target for uveitis (59). In addition, studies have shown that miRNA-410 is a key regulator of the pathogenesis of SLE, and it regulates IL-10 expression by targeting STAT3 (64). ...
... Therefore, the regulatory effect of miRNA on IL-10 can be applied to many diseases that show changes in IL-10 levels, for the treatment or prognosis of diseases. Serum miRNA-146a and miRNA-150 can be used as biomarkers for diagnosis and prediction of ALI (46), and rno-miRNA-30b-5p is a new therapeutic target for uveitis (59). It is worth noting that miRNA-98 can be involved in the treatment of various diseases, such as lung cancer, liver cancer and other tumors, as well as myocarditis and allergic diseases (61,62,64,71). ...
IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an important role in autoimmune diseases, inflammatory diseases and cancer. IL-10 is closely related to epigenetic modification, in which changes in DNA methylation of IL-10 gene can affect mRNA and protein levels of IL-10. In addition, changes in histone modifications, especially histone acetylation, can also lead to abnormal expression of IL-10 mRNA. At the same time, a handful of IL-10 related microRNAs (miRNAs) are found to be aberrantly expressed in multiple diseases. Besides, long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) also inhibits IL-10 expression. Here, we reviewed the epigenetic changes related to IL-10 in various diseases, as well as the regulation of IL-10 gene expression in various diseases by epigenetic modifications such as DNA methylation, histone modification, miRNA, and lncRNA.
