Evidence map›Paper›PMID 33534941›Full record

ArticleImmunity, inflammation and disease2021

Ruxolitinib inhibits poly(I:C) and type 2 cytokines-induced CCL5 production in bronchial epithelial cells: A potential therapeutic agent for severe eosinophilic asthma.

Mitsuru Sada, Masato Watanabe, Toshiya Inui, Keitaro Nakamoto, Aya Hirata, Masuo Nakamura, Kojiro Honda, Takeshi Saraya, Daisuke Kurai, Hirokazu Kimura and 2 more

Open access · goldAbstract read
In one paragraph

Article in Immunity, inflammation and disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Animals : an open access journal from MDPI · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. JAK inhibitors for asthma.The Journal of allergy and clinical immunology · 2021
    Review
  14. 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 2 institutions in 1 country.

Mitsuru SadaDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0002-1088-2954
Masato WatanabeDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0001-9988-5221
Toshiya InuiDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Keitaro NakamotoDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0002-7140-6273
Aya HirataDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Masuo NakamuraDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Kojiro HondaDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Takeshi SarayaDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0003-0502-8128
Daisuke KuraiDivision of Infectious Diseases, Department of General Medicine, School of Medicine, Kyorin University, Tokyo, Japan.
Hirokazu KimuraDepartment of Health Science, Graduate School of Health Science, Gunma Paz University, Gunma, Japan.
Haruyuki IshiiDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0002-9435-9246
Hajime TakizawaDepartment of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.ORCID 0000-0003-3207-8673
Kyorin University · JPGumma Paz College · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleSevere eosinophilic asthma is characterized by airway eosinophilia and corticosteroid-resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C-C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus-associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib.

methodsWe stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS-2B cells with poly(I:C) along with interleukin-13 (IL-13) or IL-4, and assessed CCL5 production. We also evaluated the signals involved in virus- and Th2-cytokine-induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production.

resultsPoly(I:C) stimulated NHBE and BEAS-2B cells to produce CCL5. Poly(I:C) and IL-13 increased CCL5 production. Poly(I:C)-induced CCL5 production occurred via the TLR3-IRF3 and IFNAR/JAK1-phosphoinositide 3-kinase (PI3K) pathways, but not the IFNAR/JAK1-STATs pathway. In addition, IL-13 did not augment poly(I:C)-induced CCL5 production via the canonical IL-13R/IL-4R/JAK1-STAT6 pathway but likely via subsequent TLR3-IRF3-IFNAR/JAK1-PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS-2B cells than fluticasone propionate.

conclusionWe have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid-resistant asthma with airway eosinophilia and persistent Th2-type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy.

Indexed as

AsthmaCytokinesBronchiChemokine CCL5Epithelial CellsHumansNitrilesPhosphatidylinositol 3-KinasesPyrazolesPyrimidinesCCL5 protein, humanChemokine CCL5CytokinesNitrilesPhosphatidylinositol 3-KinasesPyrazolesPyrimidinesruxolitinibbronchial epitheliumCCL5eosinophilic asthmaIL-13ruxolitinib

Identifiers

PMID33534941
PMCPMC8127547
OpenAlexW3126817968

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.