Evidence map›Paper›PMID 25705851›Full record

ArticleThe Journal of investigative dermatology2015

Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation.

Caroline Stremnitzer, Krisztina Manzano-Szalai, Anna Willensdorfer, Philipp Starkl, Mario Pieper, Peter König, Michael Mildner, Erwin Tschachler, Ursula Reichart, Erika Jensen-Jarolim

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Research Progress on Bioactive Factors against Skin Aging.International journal of molecular sciences · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Cell Dissociation Techniques in Salamanders.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. A WAO - ARIA - GAThe World Allergy Organization journal · 2020
    Article
  18. Article
  19. Article
  20. Best Practices for Preparing a Single Cell Suspension from Solid Tissues for Flow Cytometry.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2019
    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

10 authors at 4 institutions in 2 countries.

Caroline Stremnitzer *Department of Pathophysiology and Allergy Research, Comparative Immunology and Oncology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Krisztina Manzano-Szalai *Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University of Vienna and University Vienna, Vienna, Austria.
Anna WillensdorferComparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University of Vienna and University Vienna, Vienna, Austria.
Philipp StarklDepartment of Pathophysiology and Allergy Research, Comparative Immunology and Oncology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Mario PieperInstitute of Anatomy, University of Lübeck, Lübeck, Germany and Airway Research Center North, Member of the German Center for Lung Research (DZL), Germany.
Peter KönigInstitute of Anatomy, University of Lübeck, Lübeck, Germany and Airway Research Center North, Member of the German Center for Lung Research (DZL), Germany.
Michael MildnerDepartment of Dermatology, Medical University of Vienna, Vienna, Austria.
Erwin TschachlerDepartment of Dermatology, Medical University of Vienna, Vienna, Austria.
Ursula ReichartInstitute of Animal Breeding and Genetics and Biomodels Austria, University of Veterinary Medicine Vienna, Vienna, Austria.
Erika Jensen-JarolimDepartment of Pathophysiology and Allergy Research, Comparative Immunology and Oncology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Medical University of Vienna · ATUniversity of Veterinary Medicine Vienna · ATGerman Center for Lung Research · DEUniversity of Lübeck · DE

Funding

Austrian Science Fund FWF F 4606
6 · The paper itself

Abstract

Papain is commonly used in food, pharmaceutical, textile, and cosmetic industries and is known to induce occupational allergic asthma. We have previously shown that the papain-like cysteine protease Dermatophagoides pteronyssinus 1 from house dust mite exhibits percutaneous sensitization potential. We aimed here to investigate the potential of papain itself in epicutaneous sensitization. The effects of papain on tight junction (TJ) proteins were tested in vitro in human primary keratinocytes. Using C57BL/6 wild-type and Toll-like receptor 4 (TLR4)-deficient mice, we analyzed the sensitization potential of papain, its effects on the skin barrier, and immune cell recruitment. Our results show that papain affects the skin barrier by increasing transepidermal water loss, degrading TJ proteins and inducing vasodilation. When topically applied, papain exhibited a high epicutaneous inflammatory potential by recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response. However, its high potency for specific sensitization via the skin was TLR4 independent and, in spite of its capacity to degrade epidermal TJ proteins, does not rely on its enzymatic function. From our data, we conclude that papain has all features to act as a strong allergen via the skin.

Indexed as

AnimalsBlotting, WesternCells, CulturedDisease Models, AnimalEnzyme ActivationEnzyme-Linked Immunosorbent AssayFemaleFluorescent Antibody TechniqueImmunizationImmunohistochemistryIn Vitro TechniquesKeratinocytesMast CellsMiceMice, Inbred C57BLNeutrophilsPapainTight Junction ProteinsTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID25705851
PMCPMC4471117
OpenAlexW1965817500

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.