MicroRNA-345-5p acts as an anti-inflammatory regulator in experimental allergic rhinitis via the TLR4/NF-κB pathway.

Allergic rhinitis (AR) is a common chronic condition characterized by inflammation of the nasal mucosa. The correlation of microRNAs (miRNAs) in AR has been highlighted particularly due to their roles in regulating inflammatory responses. The aim of this study was to explore the anti-inflammatory mechanism by which miR-345-5p regulates the toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in mice with AR. Initially, the putative miR-345-5p binding sites on the 3'untranslated region of TLR4 was predicted and verified. AR models were established using ovalbumin, after which the functional role of miR-345-5p in AR was determined using gain- and loss-of-function approaches. We found that miR-345-5p was poorly expressed in nasal mucosal tissues of mice with AR. Meanwhile, TLR4 expression and the TLR4/NF-κB pathway were identified to be promoted, which were then suppressed in the presence of overexpressed miR-345-5p. In addition, nasal epithelial cell apoptosis and fibrosis were inhibited in response to miR-345-5p overexpression and TLR4 silencing. Furthermore, miR-345-5p overexpression and TLR4 silencing were observed to decrease Th2 cells, expression of pro-inflammatory factors, but to increase Th1 cells and expression of anti-inflammatory factors. This study demonstrates an important role of miR-345-5p in alleviating the inflammatory response in mice with AR by inhibiting the TLR4/NF-κB pathway. Therefore, a better understanding of this process may aid in the development of novel therapeutic agents of AR.

Liu J ，Jiang Y ，Han M ，Jiang L ，Liang D ，Li S ，Xu Z ，Wang L ，Li N ... -  《-》

Overexpression of miR-224-5p alleviates allergic rhinitis in mice via the TLR4/MyD88/NF-κB pathway.

Wu J ，Wu L ，Zhang L ，Xu H ，Wang M ，Wang L ，Chen J ，Sun K ... -  《-》

Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential. In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of β-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-κB (NF-κB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4+ IFN-γ+ ) / Th2 (CD4+ IL-4+ ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry. Apigenin significantly inhibited compound 48/80-induced secretion of β-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-κB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as β-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice. Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-κB signaling pathway.

Li H ，Zhang H ，Zhao H 《-》

MiR-146a mimic attenuates murine allergic rhinitis by downregulating TLR4/TRAF6/NF-κB pathway.

Wang J ，Cui Z ，Liu L ，Zhang S ，Zhang Y ，Zhang Y ，Su H ，Zhao Y ... -  《-》

Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway.

The prevalence of allergic rhinitis is high, making it a relatively common chronic condition. Countless patients suffer from seasonal Allergic rhinitis (AR). The objective of this investigation is to examine the potential involvement of common pollen allergens in seasonal allergic rhinitis, and study the proposed mechanism of Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the induction of AR. A mouse AR model (sensitized group) was constructed with pollen extracts and ovalbumin (OVA) of Artemisia annua (An), Artemisia argyi (Ar) and Artemisia Sieversiana (Si), and thereafter, AR symptom score was performed. After successful modeling, mouse serum and nasal mucosa tissues were extracted for subsequent experiments. The expression levels of immunoglobulin E (IgE), Interleukin (IL)-4, IL-5, IL-13 and Tumor Necrosis Factor-α (TNF-α) in serum were detected using Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E) staining methods were used to observe the pathological changes of the nasal mucosal tissue; Utilizing immunohistochemistry (IHC) staining, the expression levels of TLR4, MyD88 and Nuclear factor kappa B (NF-κB) p65 in mouse nasal mucosa were quantified; The mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of sensitized mice were detected with Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Finally, the in vitro culture of Human nasal mucosal epithelial cells (HNEpC) cells was conducted, and cells were treated with 200 µg/ml Artemisia annua pollen extract and OVA for 24 h. Western Blot assay was used to detect the expression level of TLR4, MyD88 and NF-κB p65 proteins before and after HNEpC cells were treated with MyD88 inhibitor ST-2825. On the second day after AR stimulation, the mice showed obvious AR symptoms. H&E results showed that compared to the control group, the nasal mucosal tissue in the sensitized group was significantly more inflamed. Furthermore, ELISA assay showed increased expression levels of IgE, IL-4, IL-5, IL-13 and TNF-α in serum of mice induced by OVA and Artemisia annua pollen, Artemisia argyi pollen and Artemisia Sieversiana pollen than those of the control group. However, the expression level of IL-2 was lower than that of the control group (P < 0.05). Using Immunohistochemistry staining visually observed the expression levels of TLR4, MyD88 and NF-κB p65 in mouse nasal mucosa tissues and quantitatively analyzed. The expression levels of TLR4, MyD88 and NF-κB p65 in the sensitized group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The results from qRT-PCR and Western Blot showed that the mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of the sensitized group were significantly higher than those in the control group (P < 0.05). Finally, HNEpC cells were cultured in vitro and analyzed using Western Blot. The expression levels of TLR4, MyD88 and NF-κB p65 in OVA and An groups were significantly increased (P < 0.05). After ST-2825 treatment, TLR4 protein expression was significantly increased (P < 0.05) and MyD88 and NF-κB p65 protein expression were significantly decreased (P < 0.05). To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

Zhang J ，Gao L ，Yu D ，Song Y ，Zhao Y ，Feng Y ... -  《-》