Evidence map›Paper›PMID 24796797›Full record

ArticleCell stress & chaperones2014

Hsp90 blockade modulates bullous pemphigoid IgG-induced IL-8 production by keratinocytes.

Stefan Tukaj, Denise Grüner, Detlef Zillikens, Michael Kasperkiewicz

Open access · bronzeAbstract read
In one paragraph

Article in Cell stress & chaperones, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 33 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Stefan TukajDepartment of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Denise Grüner
Detlef Zillikens
Michael Kasperkiewicz
University of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering skin disease characterized by autoantibodies against the hemidesmosomal proteins BP180 and BP230. The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses, and recent evidence suggests that it represents a novel treatment target in autoimmune bullous diseases. The aim of the study was to investigate the contribution of Hsp90 to the proinflammatory cytokine production in keratinocytes induced by autoantibodies to BP180 from BP patient serum. HaCaT cells were treated with purified human BP or normal IgG in the absence or presence of the Hsp90 blocker 17-DMAG and effects on viability, interleukin 6 (IL-6) and IL-8 (cytokines critical for BP pathology), NFκB (their major transcription factor), and Hsp70 (marker of effective Hsp90 inhibition and potent negative regulator of inflammatory responses) were investigated. We found that BP IgG stimulated IL-6 and IL-8 release from HaCaT cells and that non-toxic doses of 17-DMAG inhibited this IL-8, but not IL-6 secretion in a dose- and time-dependent fashion. Inhibition of this IL-8 production was also observed at the transcriptional level. In addition, 17-DMAG treatment blunted BP IgG-mediated upregulation of NFκB activity and was associated with Hsp70 induction. This study provides important insights that Hsp90 is involved as crucial regulator in anti-BP180 IgG-induced production of keratinocyte-derived IL-8. By adding to the knowledge of the multimodal anti-inflammatory effects of Hsp90 blockade, our data further support the introduction of Hsp90 inhibitors into the clinical setting for treatment of autoimmune diseases, especially for BP.

Indexed as

Anti-Inflammatory AgentsAutoantibodiesAutoantigensBenzoquinonesCell LineCollagen Type XVIIDose-Response Relationship, DrugHSP90 Heat-Shock ProteinsHumansImmunoglobulin GInflammation MediatorsInterleukin-6Interleukin-8KeratinocytesLactams, MacrocyclicNF-kappa B17-(dimethylaminoethylamino)-17-demethoxygeldanamycinAnti-Inflammatory AgentsAutoantibodiesAutoantigensBenzoquinonesCollagen Type XVIICXCL8 protein, humanHSP90 Heat-Shock ProteinsIL6 protein, humanImmunoglobulin GInflammation MediatorsInterleukin-6Interleukin-8Lactams, MacrocyclicNF-kappa BNon-Fibrillar Collagens

Identifiers

PMID24796797
PMCPMC4389849
OpenAlexW2005430586

What OpenQuestion holds

Textmetadata
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Registered trials

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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.