Interleukin-1 Beta Promotes Neuronal Differentiation Through the Wnt5a/RhoA/JNK Pathway in Cortical Neural Precursor Cells

Overview

Journal Mol Brain

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2018 Jul 6

PMID 29973222

Citations 35

Authors

Shin-Young Park

Min-Jeong Kang

Joong-Soo Han

Affiliations

Soon will be listed here.

Abstract

Pro-inflammatory cytokine interleukin-1 beta (IL-1β) is a key mediator of inflammation and stress in the central nervous system (CNS), and is highly expressed in the developing brain. In this study, we investigated the possible role of IL-1β in neuronal differentiation of cortical neural precursor cells (NPCs). We showed that stimulation with IL-1β increased expression levels of neurotrophin-3 (NT3) and neurogenin 1 (Ngn1) and promoted neurite outgrowth. We also found that IL-1β increased mRNA and protein levels of Wnt5a. Knockdown of Wnt5a by transfection with Wnt5a siRNA inhibited IL-1β-induced neuronal differentiation. Moreover, IL-1β-induced Wnt5a expression was regulated by nuclear factor kappa B (NF-κB) activation, which is involved in IL-1β-mediated neuronal differentiation. To examine the role of Wnt5a in neuronal differentiation of NPCs, we exogenously added Wnt5a. We found that exogenous Wnt5a promotes neuronal differentiation, and activates the RhoA/Rho-associated kinase (ROCK)/c-jun N-terminal kinase (JNK) pathway. In addition, Wnt5a-induced neuronal differentiation was blocked by RhoA siRNA, as well as by a specific Rho-kinase inhibitor (Y27632) or a SAPK/JNK inhibitor (SP600125). Furthermore, treatment with RhoA siRNA, Y27632, or SP600125 suppressed the IL-1β-induced neuronal differentiation. Therefore, these results suggest that the sequential Wnt5a/RhoA/ROCK/JNK pathway is involved in IL-1β-induced neuronal differentiation of NPCs.

Citing Articles

Gestational autoantibody exposure impacts early brain development in a rat model of MAR autism.

McLellan J, Iosif A, Cichewicz K, Canales C, Rahbarian D, Corea M Mol Psychiatry. 2025; .

PMID: 39929953 DOI: 10.1038/s41380-025-02907-3.

Ginkgo biloba extract mediates HT22 cell proliferation and migration after oxygen-glucose deprivation/reoxygenation via regulating RhoA-ROCK2 signalling pathway.

Wang D, Zhao X, Li J, Song Y, Chen W, Cai X Metab Brain Dis. 2025; 40(1):91.

PMID: 39775993 PMC: 11706868. DOI: 10.1007/s11011-024-01502-9.

[Macrophage-Activated Products of N1115 Promote the Development of Primary Hippocampal Neurons].

Zhou Z, Jia W, Chen F, Liu M, Wang K, Liu J Sichuan Da Xue Xue Bao Yi Xue Ban. 2024; 55(5):1150-1158.

PMID: 39507971 PMC: 11536243. DOI: 10.12182/20240960504.

Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.

Yang H, Liang C, Luo J, Liu X, Wang W, Zheng K Mol Neurobiol. 2024; 61(12):10830-10844.

PMID: 38795301 PMC: 11584464. DOI: 10.1007/s12035-024-04248-8.

Anti-Inflammatory Action of Resveratrol in the Central Nervous System in Relation to Glucose Concentration-An In Vitro Study on a Blood-Brain Barrier Model.

Komorowska J, Watroba M, Bednarzak M, Grabowska A, Szukiewicz D Int J Mol Sci. 2024; 25(6).

PMID: 38542084 PMC: 10970537. DOI: 10.3390/ijms25063110.

References

Hall A, Lalli G . Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol. 2010; 2(2):a001818. PMC: 2828272. DOI: 10.1101/cshperspect.a001818. View

OLeime C, Cryan J, Nolan Y . Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis. Brain Behav Immun. 2017; 66:394-412. DOI: 10.1016/j.bbi.2017.07.153. View

Ma L, Li X, Zhang S, Yang F, Zhu G, Yuan X . Interleukin-1 beta guides the migration of cortical neurons. J Neuroinflammation. 2014; 11:114. PMC: 4084576. DOI: 10.1186/1742-2094-11-114. View

Smorodchenko A, Wuerfel J, Pohl E, Vogt J, Tysiak E, Glumm R . CNS-irrelevant T-cells enter the brain, cause blood-brain barrier disruption but no glial pathology. Eur J Neurosci. 2007; 26(6):1387-98. DOI: 10.1111/j.1460-9568.2007.05792.x. View

Boato F, Hechler D, Rosenberger K, Ludecke D, Peters E, Nitsch R . Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro. J Neuroinflammation. 2011; 8:183. PMC: 3275552. DOI: 10.1186/1742-2094-8-183. View

Billuart P, WINTER C, Maresh A, Zhao X, Luo L . Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway. Cell. 2001; 107(2):195-207. DOI: 10.1016/s0092-8674(01)00522-0. View

Weston C, Davis R . The JNK signal transduction pathway. Curr Opin Genet Dev. 2002; 12(1):14-21. DOI: 10.1016/s0959-437x(01)00258-1. View

Fujita Y, Yamashita T . Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci. 2014; 8:338. PMC: 4205828. DOI: 10.3389/fnins.2014.00338. View

Soiampornkul R, Tong L, Thangnipon W, Balazs R, Cotman C . Interleukin-1beta interferes with signal transduction induced by neurotrophin-3 in cortical neurons. Brain Res. 2007; 1188:189-97. PMC: 2409119. DOI: 10.1016/j.brainres.2007.10.051. View

10.

Loudon R, Silver L, Yee Jr H, Gallo G . RhoA-kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor. J Neurobiol. 2006; 66(8):847-67. PMC: 1525020. DOI: 10.1002/neu.20258. View

11.

Gougeon P, Lourenssen S, Han T, Nair D, Ropeleski M, Blennerhassett M . The pro-inflammatory cytokines IL-1β and TNFα are neurotrophic for enteric neurons. J Neurosci. 2013; 33(8):3339-51. PMC: 6619526. DOI: 10.1523/JNEUROSCI.3564-12.2013. View

12.

Spillane M, Gallo G . Involvement of Rho-family GTPases in axon branching. Small GTPases. 2014; 5:e27974. PMC: 4114606. DOI: 10.4161/sgtp.27974. View

13.

Lu K, Cho C, Liang C, Chen S, Liliang P, Wang S . Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats. J Thorac Cardiovasc Surg. 2007; 133(4):934-41. DOI: 10.1016/j.jtcvs.2006.11.038. View

14.

Kumawat K, Gosens R . WNT-5A: signaling and functions in health and disease. Cell Mol Life Sci. 2015; 73(3):567-87. PMC: 4713724. DOI: 10.1007/s00018-015-2076-y. View

15.

Horigane S, Ageta-Ishihara N, Kamijo S, Fujii H, Okamura M, Kinoshita M . Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKIα pathway during neuronal polarization. Mol Brain. 2016; 9:8. PMC: 4715351. DOI: 10.1186/s13041-016-0189-3. View

16.

Bertrand J, Winton M, Rodriguez-Hernandez N, Campenot R, McKerracher L . Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats. J Neurosci. 2005; 25(5):1113-21. PMC: 6725958. DOI: 10.1523/JNEUROSCI.3931-04.2005. View

17.

Rico B, Beggs H, Schahin-Reed D, Kimes N, Schmidt A, Reichardt L . Control of axonal branching and synapse formation by focal adhesion kinase. Nat Neurosci. 2004; 7(10):1059-69. PMC: 2711902. DOI: 10.1038/nn1317. View

18.

Rao T, Kuhl M . An updated overview on Wnt signaling pathways: a prelude for more. Circ Res. 2010; 106(12):1798-806. DOI: 10.1161/CIRCRESAHA.110.219840. View

19.

Ryan S, OKeeffe G, OConnor C, Keeshan K, Nolan Y . Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation. Brain Behav Immun. 2013; 33:7-13. DOI: 10.1016/j.bbi.2013.03.005. View

20.

Pineau I, Lacroix S . Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol. 2006; 500(2):267-85. DOI: 10.1002/cne.21149. View