PMID- 28662502 OWN - NLM STAT- MEDLINE DCOM- 20171107 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 42 IP - 3 DP - 2017 TI - MicroRNA-133b Ameliorates Allergic Inflammation and Symptom in Murine Model of Allergic Rhinitis by Targeting Nlrp3. PG - 901-912 LID - 10.1159/000478645 [doi] AB - BACKGROUND: Emerging evidences indicate that post-transcriptional regulation by microRNAs is critical in allergic rhinitis (AR) pathogenesis. MircroRNA-133b (miR-133b) was recently suggested as a potential predictor of AR. However, the in vivo effect of miR-133b on AR is unclear. METHODS: AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). MiR-133b agomir was then intranasally administrated to mice after OVA challenge for another 7 days. The symptom of nasal rubbing and sneezing were recorded after the last OVA challenge. Nasal mucosa tissues and serum were collected. MiR-133b expression, serum OVA-specific immunoglobulin E (IgE) concentration, proinflammatory cytokines (TNF-alpha, IL-4, IL-5, IL-10 and IFN-gamma) levels, and Nlrp3 inflammasome activation were measured by RT-PCR, ELISA, western blotting or immunohistochemistry, respectively. Histopathologic changes were evaluated using hematoxylin and eosin and Sirius red staining. The luciferase activity and protein expression of Nlrp3 were also determined. RESULTS: MiR-133b expression was significantly decreased in nasal mucosa of AR mice, which was restored by nasal administration with miR-133b agomir. Upregulation of miR-133b markedly reduced the concentration of OVA-specific IgE, the frequencies of nasal rubbing and sneezing, and the levels of cytokines (TNF-alpha, IL-4, IL-5 and IFN-gamma). Levels of IL-4, IL-5, IL-10 and IFN-gamma produced by cervical lymph node cells were significantly lowered in miR-133b agomir-treated mice. Moreover, miR-133b also appeared to strongly attenuate pathological alterations and eosinophils and mast cells infiltration in nasal mucosa. Notably, we demonstrated for the first time that miR-133b negatively regulated Nlrp3 expression through binding with the 3' untranslated region of Nlrp3. Consequently, infection of miR-133b in nasal mucosa remarkably suppressed the Nlrp3 inflammasome activation, as evidenced by reduced Nlrp3, Caspase-1, ASC, IL-18 and IL-1 expressions. CONCLUSION: MiR-133b alleviates allergic symptom in AR mice by inhibition of Nlrp3 inflammasome-meditated inflammation. These findings provide us an insight into the potential role of miR-133b in relation to AR treatment. CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel. FAU - Xiao, Lifeng AU - Xiao L FAU - Jiang, Li AU - Jiang L FAU - Hu, Qi AU - Hu Q FAU - Li, Yuru AU - Li Y LA - eng PT - Journal Article DEP - 20170626 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Cytokines) RN - 0 (MicroRNAs) RN - 0 (Mirn133 microRNA, mouse) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Animals MH - Cytokines/blood MH - Disease Models, Animal MH - Down-Regulation MH - Genetic Therapy MH - HEK293 Cells MH - Humans MH - Immunoglobulin E/blood MH - Inflammation/blood/complications/genetics/therapy MH - Mice, Inbred BALB C MH - MicroRNAs/*genetics/*therapeutic use MH - NLR Family, Pyrin Domain-Containing 3 Protein/*genetics MH - Rhinitis, Allergic/blood/complications/*genetics/*therapy MH - Up-Regulation OTO - NOTNLM OT - Allergic rhinitis OT - Inflammation OT - Nlrp3 inflammasome OT - microRNA-133b EDAT- 2017/07/01 06:00 MHDA- 2017/11/08 06:00 CRDT- 2017/06/30 06:00 PHST- 2017/02/15 00:00 [received] PHST- 2017/04/11 00:00 [accepted] PHST- 2017/07/01 06:00 [pubmed] PHST- 2017/11/08 06:00 [medline] PHST- 2017/06/30 06:00 [entrez] AID - 000478645 [pii] AID - 10.1159/000478645 [doi] PST - ppublish SO - Cell Physiol Biochem. 2017;42(3):901-912. doi: 10.1159/000478645. Epub 2017 Jun 26.