ArticleBiochimica et biophysica acta2011
Heterotrimeric Gα(i) proteins are regulated by lipopolysaccharide and are anti-inflammatory in endotoxemia and polymicrobial sepsis.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 24 citations in OpenAlex.
- Gαi1 and Gαi3 mediate IL-11-induced signal transduction and are potential therapeutic targets for LUAD.Cell death & disease · 2026Article
- Gαi3: a crucial biomarker and therapeutic target in bladder cancer.NPJ precision oncology · 2025Article
- The critical role of Gαi3 in oral squamous cell carcinoma cell growth.Cell death discovery · 2024Article
- Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.Cell death & disease · 2024Article
- YME1L overexpression exerts pro-tumorigenic activity in glioma by promoting Gαi1 expression and Akt activation.Protein & cell · 2023Article
- Identification of G protein subunit alpha i2 as a promising therapeutic target of hepatocellular carcinoma.Cell death & disease · 2023Article
- G protein inhibitory α subunit 2 is a molecular oncotarget of human glioma.International journal of biological sciences · 2023Article
- Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer.International journal of biological sciences · 2022Article
- Identification of Gαi3 as a promising target for osteosarcoma treatment.International journal of biological sciences · 2022Article
- Neuronal-driven glioma growth requires Gαi1 and Gαi3.Theranostics · 2021Article
- 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
- Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- 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
- Modulation of voltage-gated Ca2+ channels by G protein-coupled receptors in celiac-mesenteric ganglion neurons of septic rats.PloS one · 2015Article
- Article
- Treatment with LPS plus INF-γ induces the expression and function of muscarinic acetylcholine receptors, modulating NIH3T3 cell proliferation: participation of NOS and COX.British journal of pharmacology · 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
- Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function or overexpression of Gα(i2) protein.Inflammation · 2012Article
- Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling.Cell communication and signaling : CCS · 2012Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Previous studies have implicated a role of heterotrimeric Gα(i) proteins in lipopolysaccharide (LPS)-induced inflammatory responses. We hypothesized that Toll-like receptor (TLR) signaling regulates Gα(i) proteins, which are anti-inflammatory in endotoxemia and polymicrobial sepsis. RAW 264.7 cells were stimulated with LPS and the Gα(i)-GTP protein complex was immunoprecipitated with a Gα(i) protein activation assay. In subsequent in vivo studies, the Gα(i) protein inhibitor pertussis toxin (PTx) or G(i) protein agonist mastoparan (MP-7) were administrated prior to endotoxemia. LPS-induced pro-inflammatory cytokines and mortality were determined. To examine the role of Gα(i2) in sepsis, Gα(i2) (-/-) and wildtype (WT) mice were subjected to cecal ligation and puncture (CLP) and monitored every 24 h for 120 h. Other mice were sacrificed 24 h after CLP. Peritoneal fluid, blood, and tissue samples were collected. Plasma pro-inflammatory cytokine production, bacterial load in peritoneal fluid, blood and lung tissue, myeloperoxidase (MPO) activity in lung and liver and different immune cell populations in spleen were studied. We found that Gα(i) proteins are rapidly activated by LPS followed by rapid inactivation. These studies provide the first direct evidence that Gα(i) proteins are modulated by TLR signaling. In following studies, PTx augmented LPS-induced plasma TNFα, IL-6, whereas MP-7 suppressed LPS-induced TNFα and decreased LPS-induced mortality. In sepsis studies, the survival rate post-CLP was significantly decreased in the Gα(i2) (-/-) mice compared to WT mice. CLP-induced plasma TNFα, IL-6, bacterial load in peritoneal fluid, blood and lung tissue and lung and liver MPO activity were significantly increased in Gα(i2) (-/-) compared to WT mice. Gα(i2) (-/-) mice also exhibited increased Th1 and Th2 responses compared to WT mice. Taken together, Gα(i) proteins are activated by LPS and negatively regulate endotoxemia and sepsis. Understanding the role of Gα(i2) protein in regulation of the inflammatory response in sepsis may provide novel targets for treatment of sepsis.
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