Evidence map›Paper›PMID 30231870›Full record

ArticleJournal of neuroinflammation2018

Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice.

Hye Yeon Nam, Jin Han Nam, Gwangho Yoon, Ju-Young Lee, Youngpyo Nam, Hye-Jin Kang, Hyun-Ji Cho, Jeongyeon Kim, Hyang-Sook Hoe

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

139 citing papers in PubMed, 284 citations in OpenAlex.

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79 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Hye Yeon NamDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Jin Han NamDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Gwangho YoonDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Ju-Young LeeDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Youngpyo NamDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Hye-Jin KangDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Hyun-Ji ChoDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Jeongyeon KimDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Hyang-Sook HoeDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea. sookhoe72@kbri.re.kr.ORCID http://orcid.org/0000-0001-8877-8594
Korea Brain Research Institute · KR

Funding

Ministry of Science, ICT and Future Planning 18-BR-02-04, H.S.HNational Research Foundation of the Korean government 2016R1A2B4011393
6 · The paper itself

Abstract

backgroundThe FDA-approved small-molecule drug ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. However, the potential regulation of neuroinflammatory responses in the brain by ibrutinib has not been comprehensively examined.

methodsBV2 microglial cells were treated with ibrutinib (1 μM) or vehicle (1% DMSO), followed by lipopolysaccharide (LPS; 1 μg/ml) or PBS. RT-PCR, immunocytochemistry, and subcellular fractionation were performed to examine the effects of ibrutinib on neuroinflammatory responses. In addition, wild-type mice were sequentially injected with ibrutinib (10 mg/kg, i.p.) or vehicle (10% DMSO, i.p.), followed by LPS (10 mg/kg, i.p.) or PBS, and microglial and astrocyte activations were assessed using immunohistochemistry.

resultsIbrutinib significantly reduced LPS-induced increases in proinflammatory cytokine levels in BV2 microglial and primary microglial cells but not in primary astrocytes. Ibrutinib regulated TLR4 signaling to alter LPS-induced proinflammatory cytokine levels. In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways. Interestingly, ibrutinib also reduced LPS-induced BV2 microglial cell migration by inhibiting AKT signaling. Moreover, ibrutinib-injected wild-type mice exhibited significantly reduced microglial/astrocyte activation and COX-2 and IL-1β proinflammatory cytokine levels.

conclusionsOur data provide insights on the mechanisms of a potential therapeutic strategy for neuroinflammation-related diseases.

Indexed as

AdenineAnimalsAnimals, NewbornAnti-Inflammatory AgentsCell Line, TransformedCells, CulturedCulture Media, Serum-FreeCyclooxygenase 2CytokinesDisease Models, AnimalHeterocyclic Compounds, 3-RingInflammationLipopolysaccharidesMaleMiceMice, Inbred C57BLAdenineAnti-Inflammatory AgentsCulture Media, Serum-FreeCyclooxygenase 2CytokinesHeterocyclic Compounds, 3-RingibrutinibLipopolysaccharidesMK 2206PiperidinesProtein Kinase InhibitorsPtgs2 protein, mousePyrazolesPyrimidinesAKTLPSMicrogliaNeuroinflammationSTAT3

Identifiers

PMID30231870
PMCPMC6145206
OpenAlexW2891163459

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.