Evidence map›Paper›PMID 27095999›Full record

ArticleJournal of molecular signaling2015

Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4(+) T Helper Cells.

Thomas R Hynes, Evan A Yost, Cassandra M Hartle, Braden J Ott, Catherine H Berlot

Open access · diamondAbstract read
In one paragraph

Article in Journal of molecular signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Multimodal analysis definesbioRxiv : the preprint server for biology · 2025
    Article
  3. Gene Expression Profiling of Type 2 Diabetes Mellitus by Bioinformatics Analysis.Computational and mathematical methods in medicine · 2020
    Article
  4. Article
  5. 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.

Thomas R HynesWeis Center for Research, Geisinger Clinic, Danville, Pennsylvania, 17822-2623, United States of America.
Evan A YostWeis Center for Research, Geisinger Clinic, Danville, Pennsylvania, 17822-2623, United States of America.
Cassandra M HartleWeis Center for Research, Geisinger Clinic, Danville, Pennsylvania, 17822-2623, United States of America.
Braden J OttWeis Center for Research, Geisinger Clinic, Danville, Pennsylvania, 17822-2623, United States of America.
Catherine H BerlotWeis Center for Research, Geisinger Clinic, Danville, Pennsylvania, 17822-2623, United States of America.
Geisinger Medical Center · US

Funding

MOLECULAR AND CELLULAR ANALYSIS OF G PROTEIN FUNCTIONR01GM050369 · NIGMS · YALE UNIVERSITY · PI BERLOT, CATHERINE H · 2000 to 2013
$3.5M
MOLECULAR ANALYSIS OF G PROTEIN ALPHA SUBUNIT FUNCTIONSR29GM050369 · NIGMS · YALE UNIVERSITY · PI BERLOT, CATHERINE H · 1995 to 1999
–
NIGMS NIH HHS R01 GM050369NIGMS NIH HHS R29 GM050369
6 · The paper itself

Abstract

backgroundInhibition of G-protein βγ (Gβγ) signaling was found previously to enhance T cell receptor (TCR)-stimulated increases in interleukin 2 (IL-2) mRNA in CD4(+) T helper cells, suggesting that Gβγ might be a useful drug target for treating autoimmune diseases, as low dose IL-2 therapy can suppress autoimmune responses. Because IL-2 may counteract autoimmunity in part by shifting CD4(+) T helper cells away from the Type 1 T helper cell (TH1) and TH17 subtypes towards the TH2 subtype, the purpose of this study was to determine if blocking Gβγ signaling affected the balance of TH1, TH17, and TH2 cytokine mRNAs produced by CD4(+) T helper cells.

methodsGallein, a small molecule inhibitor of Gβγ, and siRNA-mediated silencing of the G-protein β1 subunit (Gβ1) were used to test the effect of blocking Gβγ on mRNA levels of cytokines in primary human TCR-stimulated CD4(+) T helper cells.

resultsGallein and Gβ1 siRNA decreased interferon-γ (IFN-γ) and IL-17A mRNA levels in TCR-stimulated CD4(+) T cells grown under TH1-promoting conditions. Inhibiting Gβγ also decreased mRNA levels of STAT4, which plays a positive role in TH1 differentiation and IL-17A production. Moreover, mRNA levels of the STAT4-regulated TH1-associated proteins, IL-18 receptor β chain (IL-18Rβ), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), lymphocyte activation gene 3 (LAG-3), natural killer cell group 7 sequence (NKG7), and oncostatin M (OSM) were also decreased upon Gβγ inhibition. Gallein also increased IL-4, IL-5, IL-9, and IL-13 mRNA levels in TCR-stimulated memory CD4(+) T cells grown in TH2-promoting conditions.

conclusionsInhibiting Gβγ to produce these shifts in cytokine mRNA production might be beneficial for patients with autoimmune diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), psoriasis, multiple sclerosis (MS), and Hashimoto's thyroiditis (HT), in which both IFN-γ and IL-17A are elevated.

Indexed as

Cytokineheterotrimeric G-protein βγ complexIFN-γIL-17ASTAT4T helper cells

Identifiers

PMID27095999
PMCPMC4831316
OpenAlexW2148878078

What OpenQuestion holds

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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.