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SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway.
Scand J Immunol 2018; 87(6):e12667SJ

Abstract

Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)-induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. The expression of SIRT1 was measured at mRNA and protein levels, and the allergic symptoms were evaluated. Protein levels of OVA-specific IgE, leukotriene C4 (LTC4), eosinophil cation protein (ECP), prostaglandin D2 (PGD2), as well as different inflammatory cytokine mediators in the serum and nasal lavage fluid (NLF), were assessed by ELISA. The effects of SIRT1 on human primary nasal epithelial cells challenged with tumour necrosis factor (TNF)-α were also evaluated by investigating the HMGB1/TLR4 signalling pathway. Administration of SIRT1 significantly alleviated OVA-induced AR symptoms with lower numbers of sneezing and nasal rubbing events, decreased levels of OVA-specific IgE, LTC4, ECP, PGD2, less inflammatory cells and downregulated levels of Th2 type cytokines. SIRT1 also reduced the genes of HMGB1/TLR4 signalling pathway in the murine model and cultured human nasal epithelial cells. Expression of SIRT1 is impaired in OVA-induced AR model. The administration of SIRT1 alleviates the allergic symptoms of mice, regulates the production of pro-inflammatory mediators predominantly produced by Th2 cells in AR and attenuates expressions of proteins relevant to HMGB1/TLR4 signalling pathway. All the results showed that SIRT1 is promising as a therapeutic agent of AR.

Authors+Show Affiliations

Department of Otolaryngology, Qingdao Municipal Hospital, Qingdao, China.Department of Otolaryngology, Qingdao Municipal Hospital, Qingdao, China.Department of Out-patient, Qingdao Municipal Hospital, Qingdao, China.Department of Respiratory, Qingdao Municipal Hospital (Eastern Campus), Qingdao, China.International Clinic, Qingdao Municipal Hospital (Eastern Campus), Qingdao, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29701897

Citation

Yuan, Y, et al. "SIRT1 Attenuates Murine Allergic Rhinitis By Downregulated HMGB 1/TLR4 Pathway." Scandinavian Journal of Immunology, vol. 87, no. 6, 2018, pp. e12667.
Yuan Y, Liu Q, Zhao J, et al. SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway. Scand J Immunol. 2018;87(6):e12667.
Yuan, Y., Liu, Q., Zhao, J., Tang, H., & Sun, J. (2018). SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway. Scandinavian Journal of Immunology, 87(6), pp. e12667. doi:10.1111/sji.12667.
Yuan Y, et al. SIRT1 Attenuates Murine Allergic Rhinitis By Downregulated HMGB 1/TLR4 Pathway. Scand J Immunol. 2018;87(6):e12667. PubMed PMID: 29701897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway. AU - Yuan,Y, AU - Liu,Q, AU - Zhao,J, AU - Tang,H, AU - Sun,J, PY - 2018/02/18/received PY - 2018/04/19/accepted PY - 2018/4/28/pubmed PY - 2018/7/6/medline PY - 2018/4/28/entrez KW - HMGB1 KW - SIRT1 KW - Th2 type cytokines KW - allergic rhinitis KW - sirtuin SP - e12667 EP - e12667 JF - Scandinavian journal of immunology JO - Scand. J. Immunol. VL - 87 IS - 6 N2 - Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)-induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. The expression of SIRT1 was measured at mRNA and protein levels, and the allergic symptoms were evaluated. Protein levels of OVA-specific IgE, leukotriene C4 (LTC4), eosinophil cation protein (ECP), prostaglandin D2 (PGD2), as well as different inflammatory cytokine mediators in the serum and nasal lavage fluid (NLF), were assessed by ELISA. The effects of SIRT1 on human primary nasal epithelial cells challenged with tumour necrosis factor (TNF)-α were also evaluated by investigating the HMGB1/TLR4 signalling pathway. Administration of SIRT1 significantly alleviated OVA-induced AR symptoms with lower numbers of sneezing and nasal rubbing events, decreased levels of OVA-specific IgE, LTC4, ECP, PGD2, less inflammatory cells and downregulated levels of Th2 type cytokines. SIRT1 also reduced the genes of HMGB1/TLR4 signalling pathway in the murine model and cultured human nasal epithelial cells. Expression of SIRT1 is impaired in OVA-induced AR model. The administration of SIRT1 alleviates the allergic symptoms of mice, regulates the production of pro-inflammatory mediators predominantly produced by Th2 cells in AR and attenuates expressions of proteins relevant to HMGB1/TLR4 signalling pathway. All the results showed that SIRT1 is promising as a therapeutic agent of AR. SN - 1365-3083 UR - https://www.unboundmedicine.com/medline/citation/29701897/SIRT1_attenuates_murine_allergic_rhinitis_by_downregulated_HMGB_1/TLR4_pathway_ L2 - https://doi.org/10.1111/sji.12667 DB - PRIME DP - Unbound Medicine ER -