Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway
Yalong Dang,1 Yalin Mu,2 Kun Wang,3 Ke Xu,2 Jing Yang,1 Yu Zhu,1 Bin Luo2,3 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People’s R...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016-02-01
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| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/papaverine-inhibits-lipopolysaccharide-induced-microglial-activation-b-peer-reviewed-article-DDDT |
| _version_ | 1818109336678825984 |
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| author | Dang Y Mu Y Wang K Xu K Yang J Zhu Y Luo B |
| author_facet | Dang Y Mu Y Wang K Xu K Yang J Zhu Y Luo B |
| author_sort | Dang Y |
| collection | DOAJ |
| description | Yalong Dang,1 Yalin Mu,2 Kun Wang,3 Ke Xu,2 Jing Yang,1 Yu Zhu,1 Bin Luo2,3 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People’s Republic of China; 3Clinical Laboratory, Yellow-River Hospital, Sanmenxia City, People’s Republic of China Objective: To investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms. Materials and methods: BV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 µg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect the location and expression of P65 and p-IKK in the presence or absence of PAP pretreatment. Results: Pretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation. Conclusion: PAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases. Keywords: papaverine, microglia, neuroprotection, neuroinflammation |
| first_indexed | 2024-12-11T02:29:38Z |
| format | Article |
| id | doaj.art-b5b6337635f34888b0bfb0555a5e5bdc |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-11T02:29:38Z |
| publishDate | 2016-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-b5b6337635f34888b0bfb0555a5e5bdc2022-12-22T01:23:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812016-02-012016Issue 185185925753Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathwayDang YMu YWang KXu KYang JZhu YLuo BYalong Dang,1 Yalin Mu,2 Kun Wang,3 Ke Xu,2 Jing Yang,1 Yu Zhu,1 Bin Luo2,3 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People’s Republic of China; 3Clinical Laboratory, Yellow-River Hospital, Sanmenxia City, People’s Republic of China Objective: To investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms. Materials and methods: BV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 µg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect the location and expression of P65 and p-IKK in the presence or absence of PAP pretreatment. Results: Pretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation. Conclusion: PAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases. Keywords: papaverine, microglia, neuroprotection, neuroinflammationhttps://www.dovepress.com/papaverine-inhibits-lipopolysaccharide-induced-microglial-activation-b-peer-reviewed-article-DDDTPapaverinemicroglianeuroprotectionneuro-inflammation. |
| spellingShingle | Dang Y Mu Y Wang K Xu K Yang J Zhu Y Luo B Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway Drug Design, Development and Therapy Papaverine microglia neuroprotection neuro-inflammation. |
| title | Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway |
| title_full | Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway |
| title_fullStr | Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway |
| title_full_unstemmed | Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway |
| title_short | Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway |
| title_sort | papaverine inhibits lipopolysaccharide induced microglial activation by suppressing nf kappa b signaling pathway |
| topic | Papaverine microglia neuroprotection neuro-inflammation. |
| url | https://www.dovepress.com/papaverine-inhibits-lipopolysaccharide-induced-microglial-activation-b-peer-reviewed-article-DDDT |
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