Evidence map›Paper›PMID 24714157›Full record

ArticlePloS one2014

Chemokine receptor CCR8 is required for lipopolysaccharide-triggered cytokine production in mouse peritoneal macrophages.

Tomoyuki Oshio, Rei Kawashima, Yuki I Kawamura, Teruki Hagiwara, Noriko Mizutani, Toshihiko Okada, Takeshi Otsubo, Kyoko Inagaki-Ohara, Akihiro Matsukawa, Tatsuya Haga and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Immunomodulatory Effects ofInternational journal of molecular sciences · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

14 authors at 6 institutions in 1 country.

Tomoyuki OshioDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan; Department of Dermatology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Rei KawashimaDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan; Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan.
Yuki I KawamuraDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Teruki HagiwaraDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Noriko MizutaniDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Toshihiko OkadaDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Takeshi OtsuboDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Kyoko Inagaki-OharaDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Akihiro MatsukawaDepartment of Pathology & Experimental Medicine, Okayama University, Okayama, Okayama, Japan.
Tatsuya HagaDepartment of Life Science, Gakushuin University, Mejiro-ku, Tokyo, Japan.
Shigeru KakutaDepartment of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yoichiro IwakuraDivision of Experimental Animal Immunology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Seijiro HosokawaDepartment of Applied Chemistry, Faculty of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, Japan.
Taeko DohiDepartment of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
National Center for Global Health and Medicine · JPGakushuin University · JPOkayama University · JPThe University of Tokyo · JPTokyo University of Science · JPWaseda University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemokine (C-C motif) receptor 8 (CCR8), the chemokine receptor for chemokine (C-C motif) ligand 1 (CCL1), is expressed in T-helper type-2 lymphocytes and peritoneal macrophages (PMφ) and is involved in various pathological conditions, including peritoneal adhesions. However, the role of CCR8 in inflammatory responses is not fully elucidated. To investigate the function of CCR8 in macrophages, we compared cytokine secretion from mouse PMφ or bone marrow-derived macrophages (BMMφ) stimulated with various Toll-like receptor (TLR) ligands in CCR8 deficient (CCR8-/-) and wild-type (WT) mice. We found that CCR8-/- PMφ demonstrated attenuated secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 when stimulated with lipopolysaccharide (LPS). In particular, LPS-induced IL-10 production absolutely required CCR8. CCR8-dependent cytokine secretion was characteristic of PMφ but not BMMφ. To further investigate this result, we selected the small molecule compound R243 from a library of compounds with CCR8-antagonistic effects on CCL1-induced Ca2+ flux and CCL1-driven PMφ aggregation. Similar to CCR8-/- PMφ, R243 attenuated secretion of TNF-α, IL-6, and most strikingly IL-10 from WT PMφ, but not BMMφ. CCR8-/- PMφ and R243-treated WT PMφ both showed suppressed c-jun N-terminal kinase activity and nuclear factor-κB signaling after LPS treatment when compared with WT PMφ. A c-Jun signaling pathway inhibitor also produced an inhibitory effect on LPS-induced cytokine secretion that was similar to that of CCR8 deficiency or R243 treatment. As seen in CCR8-/- mice, administration of R243 attenuated peritoneal adhesions in vivo. R243 also prevented hapten-induced colitis. These results are indicative of cross talk between signaling pathways downstream of CCR8 and TLR-4 that induces cytokine production by PMφ. Through use of CCR8-/- mice and the new CCR8 inhibitor, R243, we identified a novel macrophage innate immune response pathway that involves a chemokine receptor.

Indexed as

AnimalsChemokine CCL1ChemotaxisColitisCytokinesDisease Models, AnimalInflammationIntracellular SpaceLipopolysaccharidesMacrophagesMacrophages, PeritonealMaleMiceMice, KnockoutProtein TransportReceptors, CCR8Chemokine CCL1CytokinesLipopolysaccharidesReceptors, CCR8Toll-Like Receptors

Identifiers

PMID24714157
PMCPMC3979852
OpenAlexW2014320172

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.