1. Academic Validation
  2. Cascade Signals of Papaverine Inhibiting LPS-Induced Retinal Microglial Activation

Cascade Signals of Papaverine Inhibiting LPS-Induced Retinal Microglial Activation

  • J Mol Neurosci. 2019 May;68(1):111-119. doi: 10.1007/s12031-019-01289-w.
Ting Zhou 1 Yu Zhu 2
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, East Jianshe Road, Zhengzhou, 450001, People's Republic of China.
  • 2 Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, East Jianshe Road, Zhengzhou, 450001, People's Republic of China. 13673666718@163.com.
Abstract

Studies have shown that papaverine can inhibit lipopolysaccharide (LPS)-induced microglial activation. The retinal primary microglia of newborn SD rats were isolated and purified, and a LPS-induced microglia activation model was established. The protein phosphorylation level of the signaling pathway was detected by western blotting. The transcription and expression of TNF-α, IL-1β, and IL-10 were respectively detected by RT-PCR and ELISA to observe the abnormal activation of primary microglia. The cAMP inhibitor Rp-isomer, PKA Inhibitor H89, and MEK Inhibitor U0126 were separately added to further investigate the role of MEK/ERK in PAP inhibition of primary microglial activation and the relationship between cAMP/PKA and MEK/ERK. It was found that the level of MEK phosphorylation was upregulated after LPS stimulation, which was blocked by 10 μg/ml of papaverine.10μM U0126 significantly inhibited TNF-α and IL-1β and increased IL-10 transcription and expression in retinal microglia (P < 0.01). Both Rp-isomer and H89 upregulated the phosphorylation levels of MEK and ERK. Papaverine may inhibit inflammatory factors and promote the expression of anti-inflammatory factors through the cAMP/PKA and MEK/ERK pathway, thereby inhibiting LPS-induced activation of primary retinal microglia, and the MEK/ERK pathway may be partially regulated by cAMP/PKA, which can provide theoretical basis and experimental basis for its protection of the central nervous system.

Keywords

MEK/Erk; Papaverine; Primary microglia; cAMP/PKA.

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