Tags

Type your tag names separated by a space and hit enter

IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling.
Exp Cell Res. 2019 11 01; 384(1):111554.EC

Abstract

BACKGROUND

Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood.

METHODS

In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS.

RESULTS

Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation.

CONCLUSION

IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.

Authors+Show Affiliations

Medical School of South China University of Technology, Guangzhou, 510006, China. Electronic address: 1913696917@qq.com.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: zhengcj@mail2.sysu.edu.cn.Medical School of South China University of Technology, Guangzhou, 510006, China. Electronic address: zzp9463@163.com.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: 1605008192@qq.com.The Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: 147372970@qq.com.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: frankxie2000@yahoo.com.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Guangzhou, 510080, China. Electronic address: wuzhd@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31415761

Citation

Feng, Ying, et al. "IL-17A Neutralizing Antibody Attenuates Eosinophilic Meningitis Caused By Angiostrongylus Cantonensis By Involving IL-17RA/Traf6/NF-κB Signaling." Experimental Cell Research, vol. 384, no. 1, 2019, p. 111554.
Feng Y, Zheng C, Zhou Z, et al. IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling. Exp Cell Res. 2019;384(1):111554.
Feng, Y., Zheng, C., Zhou, Z., Xiong, H., Feng, F., Xie, F., & Wu, Z. D. (2019). IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling. Experimental Cell Research, 384(1), 111554. https://doi.org/10.1016/j.yexcr.2019.111554
Feng Y, et al. IL-17A Neutralizing Antibody Attenuates Eosinophilic Meningitis Caused By Angiostrongylus Cantonensis By Involving IL-17RA/Traf6/NF-κB Signaling. Exp Cell Res. 2019 11 1;384(1):111554. PubMed PMID: 31415761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling. AU - Feng,Ying, AU - Zheng,Cunjing, AU - Zhou,Zongpu, AU - Xiong,Huihui, AU - Feng,Feng, AU - Xie,Fukang, AU - Wu,Zhong-Dao, Y1 - 2019/08/12/ PY - 2019/06/19/received PY - 2019/08/08/revised PY - 2019/08/10/accepted PY - 2019/8/16/pubmed PY - 2020/6/17/medline PY - 2019/8/16/entrez KW - A. cantonensis KW - Eosinophilic meningitis KW - IL-17A neutralizing antibodies KW - IL-17RA/Traf6/NF-κB signaling pathway SP - 111554 EP - 111554 JF - Experimental cell research JO - Exp Cell Res VL - 384 IS - 1 N2 - BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. METHODS: In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. RESULTS: Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. CONCLUSION: IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM. SN - 1090-2422 UR - https://www.unboundmedicine.com/medline/citation/31415761/IL_17A_neutralizing_antibody_attenuates_eosinophilic_meningitis_caused_by_Angiostrongylus_cantonensis_by_involving_IL_17RA/Traf6/NF_κB_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(19)30406-9 DB - PRIME DP - Unbound Medicine ER -