Evidence map›Paper›PMID 26378047›Full record

ArticleOncotarget2015

Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties.

Kshitij Gupta, Akhil Kotian, Hariharan Subramanian, Henry Daniell, Hydar Ali

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
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  4. Article
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  6. Review
  7. In Vitro Evaluation of the Cytotoxic Effect ofMolecules (Basel, Switzerland) · 2022
    Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Angiogenic Host Defense Peptide AG-30/5C and Bradykinin BJournal of immunology (Baltimore, Md. : 1950) · 2019
    Article
  18. Mast cell activators as novel immune regulators.Current opinion in pharmacology · 2018
    Review
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Kshitij GuptaDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Akhil KotianDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hariharan SubramanianDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Henry DaniellDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hydar AliDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
University of Pennsylvania · US

Funding

Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Expression of Human Therapeutic Proteins in Transgenic Tobacco ChloroplastsR01GM063879 · NIGMS · UNIVERSITY OF CENTRAL FLORIDA · PI DANIELL, HENRY · 2002 to 2010
$2.0M
A novel role for the adapter molecule NHERF1 in regulating asthma and allergic reR00HL121073 · NHLBI · MICHIGAN STATE UNIVERSITY · PI SUBRAMANIAN, HARIHARAN · 2016 to 2018
$734k
Human mast cell-specific Mas-related Gene-X2 (MrgX2) in Anaphylaxis and AsthmaR21AI108585 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2014 to 2015
$440k
A novel role for the adapter molecule NHERF1 in regulating asthma and allergic reK99HL121073 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SUBRAMANIAN, HARIHARAN · 2014 to 2015
$216k
NHLBI NIH HHS K99 HL121073NHLBI NIH HHS K99-HL121073NHLBI NIH HHS R00 HL121073NHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01-HL107904NHLBI NIH HHS R01 HL109442NHLBI NIH HHS R01-HL109442NIAID NIH HHS AI108585NIAID NIH HHS R21 AI108585NIGMS NIH HHS R01 GM063879
6 · The paper itself

Abstract

Preclinical evaluation of Retrocyclins (RC-100, RC-101) and Protegrin-1 (PG-1) antimicrobial peptides (AMPs) is important because of their therapeutic potential against bacterial, fungal and viral infections. Human mast cells (HMCs) play important roles in host defense and wound healing but the abilities of retrocyclins and protegrin-1 to harness these functions have not been investigated. Here, we report that chemically synthesized RC-100 and PG-1 caused calcium mobilization and degranulation in HMCs but these responses were not blocked by an inhibitor of formyl peptide receptor-like 1 (FPRL1), a known receptor for AMPs. However, RC-100 and PG-1 induced degranulation in rat basophilic leukemia (RBL-2H3) cells stably expressing Mas related G protein coupled receptor X2 (MrgX2). Chemical synthesis of these AMPs is prohibitively expensive and post-synthesis modifications (cyclization, disulfide bonds, folding) are inadequate for optimal antimicrobial activity. Indeed, we found that synthetic RC-100, which caused mast cell degranulation via MrgX2, did not display any antimicrobial activity. Green-fluorescent protein (GFP)-tagged RC-101 (analog of RC-100) and GFP-tagged PG-1 purified from transgenic plant chloroplasts killed bacteria and induced mast cell degranulation. Furthermore, GFP-PG1 bound specifically to RBL-2H3 cells expressing MrgX2. These findings suggest that retrocyclins and protegrins activate HMCs independently of FPRL1 but via MrgX2. Harnessing this novel feature of AMPs to activate mast cell's host defense/wound healing properties in addition to their antimicrobial activities expands their clinical potential. Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems.

Indexed as

AnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacteriaCalcium SignalingCell DegranulationCell Line, TumorDefensinsDose-Response Relationship, DrugHumansImmunologic FactorsMast CellsMicrobial ViabilityNerve Tissue ProteinsPlants, Genetically ModifiedRatsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesDefensinsImmunologic FactorsMRGPRX2 protein, humanNerve Tissue Proteinsprotegrin-1Receptors, G-Protein-CoupledReceptors, NeuropeptideRecombinant Fusion Proteinstheta-defensinantimicrobial peptideschloroplastImmune responseImmunityImmunology and Microbiology Sectionmast cellsMrgX2protegrinretrocyclin

Identifiers

PMID26378047
PMCPMC4745678
OpenAlexW1854892167

What OpenQuestion holds

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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.