ArticleInflammation2012
Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function or overexpression of Gα(i2) protein.
Article in Inflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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.
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.
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells.Journal of translational medicine · 2025Article
- A preliminary study: proteomic analysis of exosomes derived from thyroid-stimulating hormone-stimulated HepG2 cells.Journal of endocrinological investigation · 2020Article
- GαJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Chromatin remodeling: demethylating H3K4me3 of type I IFNs gene by Rbp2 through interacting with Piasy for transcriptional attenuation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Proinflammatory switch from Gαs to Gαi signaling by Glucagon-like peptide-1 receptor in murine splenic monocyte following burn injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity.Biochemical pharmacology · 2016Review
- Spontaneous and transgenic rodent models of inflammatory bowel disease.Laboratory animal research · 2015Review
- Gαi1 and Gαi3 regulate macrophage polarization by forming a complex containing CD14 and Gab1.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan.Molecular and cellular biology · 2014Article
- Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in the absence of allergic inflammation.The Journal of allergy and clinical immunology · 2014Article
- Vitamin d deficiency reduces the immune response, phagocytosis rate, and intracellular killing rate of microglial cells.Infection and immunity · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Previous studies have implicated a role of Gα(i) proteins as co-regulators of Toll-like receptor (TLR) activation. These studies largely derived from examining the effect of Gα(i) protein inhibitors or genetic deletion of Gα(i) proteins. However, the effect of increased Gα(i) protein function or Gα(i) protein expression on TLR activation has not been investigated. We hypothesized that gain of function or increased expression of Gα(i) proteins suppresses TLR2- and TLR4-induced inflammatory cytokines. Novel transgenic mice with genomic "knock-in" of a regulator of G protein signaling (RGS)-insensitive Gnai2 allele (Gα(i2)(G184S/G184S) ; GS/GS) were employed. These mice express essentially normal levels of Gα(i2) protein; however, the Gα(i2) is insensitive to its negative regulator RGS thus rendering more sustained Gα(i2) protein activation following ligand/receptor binding. In subsequent studies, we generated Raw 264.7 cells that stably overexpress Gα(i2) protein (Raw Gα(i2)). Peritoneal macrophages, splenocytes, and mouse embryonic fibroblasts (MEF) were isolated from WT and GS/GS mice and were stimulated with LPS, Pam3CSK4, or Poly (I:C). We also subjected WT and GS/GS mice to endotoxic shock (LPS, 25 mg/kg i.p.) and plasma tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 production were determined. We found that in vitro LPS and Pam3CSK4-induced TNF-α, and IL-6 production are decreased in macrophages from GS/GS mice compared with WT mice (p < 0.05). In vitro, LPS and Pam3CSK4 induced IL-6 production in splenocytes, and in vivo, LPS-induced IL-6 were suppressed in GS/GS mice. Poly (I:C)-induced TNF-α, and IL-6 in vitro demonstrated no difference between GS/GS mice and WT mice. LPS-induced IL-6 production was inhibited in MEFs from GS/GS mice similarly to macrophage and splenocytes. In parallel studies, Raw Gα(i2) cells also exhibit decreased TNF-α and IL-6 production in response to LPS and Pam3CSK4. These studies support our hypothesis that Gα(i2) proteins are novel negative regulators of TLR activation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.