Evidence map›Paper›PMID 26113114›Full record

ArticleJournal of dermatological science2015

Sphingosine kinase 1 activation enhances epidermal innate immunity through sphingosine-1-phosphate stimulation of cathelicidin production.

Se Kyoo Jeong, Young Il Kim, Kyong-Oh Shin, Bong-Woo Kim, Sin Hee Lee, Jeong Eun Jeon, Hyun Jong Kim, Yong-Moon Lee, Theodora M Mauro, Peter M Elias and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of dermatological science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Topical Application of S1PBiomolecules & therapeutics · 2020
    Article
  7. Article
  8. Review
  9. Review
  10. Article
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

12 authors at 3 institutions in 2 countries.

Se Kyoo JeongCRID center, NeoPharm Co., Ltd., Daejeon 305-510, South Korea; College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Young Il KimDepartment of Dermatology, School of Medicine, University of California, San Francisco, CA 94158, USA; Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Northern California Institute for Research and Education, San Francisco, CA 94121, USA.
Kyong-Oh ShinCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Bong-Woo KimCRID center, NeoPharm Co., Ltd., Daejeon 305-510, South Korea.
Sin Hee LeeCRID center, NeoPharm Co., Ltd., Daejeon 305-510, South Korea.
Jeong Eun JeonCRID center, NeoPharm Co., Ltd., Daejeon 305-510, South Korea.
Hyun Jong KimDepartment of Dermatology and Atopy Clinic, Seoul Medical Center, Seoul 131-865, South Korea.
Yong-Moon LeeCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Theodora M MauroDepartment of Dermatology, School of Medicine, University of California, San Francisco, CA 94158, USA; Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Northern California Institute for Research and Education, San Francisco, CA 94121, USA.
Peter M EliasDepartment of Dermatology, School of Medicine, University of California, San Francisco, CA 94158, USA; Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Northern California Institute for Research and Education, San Francisco, CA 94121, USA.
Yoshikazu UchidaDepartment of Dermatology, School of Medicine, University of California, San Francisco, CA 94158, USA; Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Northern California Institute for Research and Education, San Francisco, CA 94121, USA. Electronic address: uchiday@derm.ucsf.edu.
Kyungho ParkDepartment of Dermatology, School of Medicine, University of California, San Francisco, CA 94158, USA; Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Northern California Institute for Research and Education, San Francisco, CA 94121, USA. Electronic address: parkk@derm.ucsf.edu.
University of California, San Francisco · USChungbuk National University · KRSan Francisco VA Medical Center · US

Funding

ATP2A2-Regulated Keretinocyted Ca2+ Signaling MechanismsR01AR051930 · NIAMS · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MAURO, THEODORA M · 2006 to 2019
$3.2M
S1P-Mediated Stimulation of Antimicrobial DefenseR01AR062025 · NIAMS · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI HOLLERAN, WALTER M · 2012 to 2016
$1.6M
NIAMS NIH HHS AR062025NIAMS NIH HHS R01 AR051930NIAMS NIH HHS R01 AR062025
6 · The paper itself

Abstract

backgroundThe ceramide metabolite, sphingosine-1-phosphate (S1P), regulates multiple cellular functions in keratinocytes (KC). We recently discovered that production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), is stimulated via a NF-κB-dependent mechanism that is activated by S1P when S1P is generated by sphingosine kinase (SPHK) 1.

objectiveWe investigated whether pharmacological modulation of SPHK1 activity, using a novel synthetic SPHK1 activator, (S)-methyl 2-(hexanamide)-3-(4-hydroxyphenyl) propanoate (MHP), stimulates CAMP expression.

methodsMHP-mediated changes in both S1P and CAMP downstream mediators were analyzed in normal cultured human KC by qRT-PCR, Western immunoblot, ELISA, confocal microscopy for immunohistochemistry, HPLC and ESI-LC/MS/MS, and microbial pathogen invasion/colonization in a human epidermal organotypic model.

resultsTreatment with MHP directly activated SPHK1 and increased cellular S1P content in normal cultured human KC. Because MHP did not inhibit S1P lyase activity, which hydrolyses S1P, augumented S1P levels could be attributed to increased synthesis rather than blockade of S1P degradation. Next, we found that exogenous MHP significantly stimulated CAMP mRNA and protein production in KC, increases that were significantly suppressed by siRNA directed against SPHK1, but not by a scrambled control siRNA. NF-κB activation, assessed by nuclear translocation of NF-κB, occurred in cells following incubation with MHP. Conversely, pretreatment with a specific inhibitor of SPHK1 decreased MHP-induced nuclear translocation of NF-κB, and significantly attenuated the MHP-mediated increase in CAMP production. Finally, topical MHP significantly suppressed invasion of the virulent Staphylococcus aureus into murine skin explants.

conclusionMHP activation of SPHK1, a target enzyme of CAMP production, can stimulate innate immunity.

Indexed as

Immunity, InnateAnimalsAntimicrobial Cationic PeptidesBacterial Physiological PhenomenaCathelicidinsCells, CulturedEnzyme ActivatorsEnzyme InhibitorsEpidermisHumansKeratinocytesLysophospholipidsMiceNF-kappa BPhosphotransferases (Alcohol Group Acceptor)RNA, MessengerAntimicrobial Cationic PeptidesCathelicidinsEnzyme ActivatorsEnzyme InhibitorsLysophospholipidsmethyl 2-(hexanamide)-3-(4-hydroxyphenyl)propanoateNF-kappa BPhosphotransferases (Alcohol Group Acceptor)RNA, MessengerRNA, Small InterferingSphingosinesphingosine 1-phosphateSphingosine KinaseTyrosineAntimicrobial defenseCathelicidin antimicrobial peptideSmall moleculeSphingosine kinase 1

Identifiers

PMID26113114
PMCPMC4624019
OpenAlexW2106735399

What OpenQuestion holds

Textmetadata
LicenceTDM
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.