Evidence map›Paper›PMID 40082319›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025

Vitamin D3 suppresses NLRP3 inflammasome pathway and enhances steroid sensitivity in a neutrophilic steroid hyporesponsive asthma mouse model.

Bariaa Khalil, Narjes Saheb Sharif-Askari, Balachandar Selvakumar, Bushra Mdkhana, Ibrahim Hachim, Adel Zakri, Jennifer Hundt, Qutayba Hamid, Rabih Halwani

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

9 authors.

Bariaa KhalilResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Narjes Saheb Sharif-AskariResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Balachandar SelvakumarResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Bushra MdkhanaResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Ibrahim HachimResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Adel ZakriDepartment of Plant Production, Faculty of Agriculture and Food Sciences, King Saud University, Riyadh, Saudi Arabia.
Jennifer HundtLübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany.
Qutayba HamidResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Rabih HalwaniResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. Rhalwani@sharjah.ac.ae.

Funding

King Saud University RSPD2024R1089
6 · The paper itself

Abstract

objectiveSevere steroid hyporesponsive asthma is a heterogeneous group of chronic inflammatory diseases characterized by irreversible airflow limitation, hyperresponsiveness, inflammation, and remodelling of the airways. Severe asthmatics account for more than 60% of asthma-related healthcare cost worldwide given they are hyporesponsive to corticosteroids and due to the absence of targeted treatment specifically for the T helper-17 (Th-17) high endotype. Hence, there is a clear unmet need to investigate other treatment options to control patients' symptoms. The role of the NLRP3 inflammasome pathway has been highlighted in the literature to contribute to disease pathogenesis and severity. Interestingly, vitamin D3 is an important regulator of the NLRP3 inflammasome pathway.

methodsUsing house dust mite (HDM) and lipopolysaccharide (LPS), we induced a neutrophilic steroid hyporesponsive asthma mouse model to investigate the effect of vitamin D3 on downregulating the NLRP3 inflammasome pathway and enhancing steroid sensitivity.

resultsWe showed that calcitriol, the active form of vitamin D3, could downregulate the NLRP3 inflammasome pathway. This was associated with a significant reduction in airway hyperresponsiveness, IL-17 release, neutrophil infiltration, and mucus secretion. Further, calcitriol enhanced steroid sensitivity by inhibiting the expression of GR-β. Mechanistically, calcitriol targeted the NLRP3 inflammasome to ubiquitination.

conclusionsOur research highlights the potential use of calcitriol as a low cost and accessible supplement to ameliorate airway inflammation during severe steroid hyporesponsive asthma.

Indexed as

AsthmaCalcitriolCholecalciferolInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsDisease Models, AnimalFemaleInterleukin-17LipopolysaccharidesLungMaleMiceMice, Inbred BALB CNeutrophilsPyroglyphidaeCalcitriolCholecalciferolInflammasomesInterleukin-17LipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseNeutrophilic airway inflammationNLRP3 inflammasomeSevere asthmaSteroid resistanceVitamin D3

Identifiers

PMID40082319

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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.