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Guo Wei

Publications and source records attributed to Guo Wei.

At least 19 recordsLinked to original sources
PubMed2026

Metagenomic next-generation sequencing for tuberculosis diagnosis: enhanced performance and cost-effectiveness.

UNLABELLED: Metagenomic next-generation sequencing (mNGS) is a promising tool for diagnosing challenging infections like tuberculosis (TB). However, previous studies largely focused on case-specific application of mNGS in TB diagnosis. Thus, we conducted a retrospective observational study to first systematically evaluate the diagnostic performance and cost-effectiveness of mNGS for TB diagnosis. We retrieved a total of 16,776 results of the seven TB diagnostic assays, including mNGS, tuberculosis IgG antibody, TB interferon-γ release assay (TB-IGRA), TB-DNA, Xpert MTB/RIF (Xpert), culture, and acid-fast bacilli staining (AFS) from 3,757 participants with suspected TB infection at Sichuan Provincial People's Hospital from September 2021 to July 2024. Diagnostic metrics were compared against a composite reference standard. Microbial composition and a cost-utility analysis were performed. Among seven TB assays studied, the World Health Organization (WHO)-recommended assays AFS, culture, and Xpert, as well as TB-IGRA, were requested most frequently for TB diagnosis, whereas mNGS ranked last. mNGS demonstrated the highest specificity (100%), accuracy (72.3%), and area under the curve (AUC) (0.795). Its sensitivity in bronchoalveolar lavage fluid and tissue was 71.0% and 72.7%, respectively. Sequential use of mNGS after initial WHO-recommended tests (Xpert/Culture/AFS) significantly improved diagnostic performance (sensitivity, 70.4%; AUC, 0.823). Microbial analysis associated Candida albicans with TB. Cost-utility analysis showed sequential mNGS became cost-effective at higher willingness-to-pay thresholds (>200,000 RMB per correct diagnosis). mNGS offers superior specificity for TB diagnosis. A sequential strategy applying mNGS to conventional-test-negative cases provides enhanced diagnostic performance and is cost-effective at higher healthcare investment values, supporting its utility for diagnostically challenging TB. IMPORTANCE: This study systematically assesses the diagnostic performance and cost utility of metagenomic next-generation sequencing (mNGS) for tuberculosis (TB) in a large real-world cohort of 3,757 suspected patients, comparing it against six conventional assays (tuberculosis IgG antibody, TB interferon-γ release assay, TB-DNA, Xpert, culture, and acid-fast bacilli staining). mNGS demonstrated the highest specificity (100%), accuracy (72.3%), and area under the curve (AUC) (0.795), with sensitivities of 71.0% in bronchoalveolar lavage fluid and 72.7% in tissue. Notably, sequential use of mNGS after the World Health Organization-recommended tests significantly improved sensitivity to 70.4% and AUC to 0.823. Candida albicans showed significant differences among the three groups. The sequential mNGS strategy was cost-effective compared with no mNGS, and its cost-effectiveness increased with a rising willingness-to-pay threshold. Overall, these results highlight mNGS as a valuable supplementary tool for challenging TB cases, especially when conventional tests are inconclusive, and provide strong evidence for integrating it into diagnostic algorithms to optimize clinical decision-making and resource allocation.

Adult↗
PubMed2026

Genome- and peak-informed two-stage framework for scATAC-seq cell type identification.

MOTIVATION: Accurate cell type annotation is essential in scATAC-seq analysis, as it underpins the characterization of cellular heterogeneity, the identification of regulatory elements, and downstream biological discovery. However, current annotation methods still face major challenges. First, although some approaches attempt to integrate genomic sequence information, they typically rely on shallow sequence representations and thus fail to capture the long-range dependencies and regulatory signals encoded in DNA. Second, substantial batch effects introduced by different platforms, sequencing batches, or tissue sources remain insufficiently addressed. Existing models often lack robust distribution alignment and domain generalization capabilities, leading to confounding non-biological variation and reduced annotation accuracy across datasets. RESULTS: To overcome these limitations, we propose seqAlignATAC, a two-stage intra-modality annotation framework that integrates sequence-derived embeddings with domain adaptation. In the first stage, we employ a large-scale pretrained nucleotide language model to extract low-dimensional, biologically informative representations from the genomic sequences of chromatin-accessible peaks. In the second stage, these embeddings are fed into a supervised neural network equipped with an adaptive alignment module to mitigate batch effects and harmonize feature distributions between labeled reference and unlabeled target datasets. Extensive experiments across multiple settings demonstrate that seqAlignATAC achieves competitive accuracy and robustness, effectively leveraging genome-level information while alleviating batch-induced distributional discrepancies. AVAILABILITY AND IMPLEMENTATION: The source code of seqAlignATAC is available at: https://github.com/BioCS-Lab/seqAlignATAC.

Humans↗
PubMed2025

A Graph Contrastive Learning Method for Enhancing Genome Recovery in Complex Microbial Communities.

Accurate genome binning is essential for resolving microbial community structure and functional potential from metagenomic data. However, existing approaches-primarily reliant on tetranucleotide frequency (TNF) and abundance profiles-often perform sub-optimally in the face of complex community compositions, low-abundance taxa, and long-read sequencing datasets. To address these limitations, we present MBGCCA, a novel metagenomic binning framework that synergistically integrates graph neural networks (GNNs), contrastive learning, and information-theoretic regularization to enhance binning accuracy, robustness, and biological coherence. MBGCCA operates in two stages: (1) multimodal information integration, where TNF and abundance profiles are fused via a deep neural network trained using a multi-view contrastive loss, and (2) self-supervised graph representation learning, which leverages assembly graph topology to refine contig embeddings. The contrastive learning objective follows the InfoMax principle by maximizing mutual information across augmented views and modalities, encouraging the model to extract globally consistent and high-information representations. By aligning perturbed graph views while preserving topological structure, MBGCCA effectively captures both global genomic characteristics and local contig relationships. Comprehensive evaluations using both synthetic and real-world datasets-including wastewater and soil microbiomes-demonstrate that MBGCCA consistently outperforms state-of-the-art binning methods, particularly in challenging scenarios marked by sparse data and high community complexity. These results highlight the value of entropy-aware, topology-preserving learning for advancing metagenomic genome reconstruction.

canonical correlation analysis↗
PubMed2006

The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.

To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.

Alzheimer Disease↗
PubMed2006

Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance.

Drug resistance remains a major obstacle to successful cancer treatment. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in acute lymphoblastic leukemia (ALL) cells. The screen indicated that the mTOR inhibitor rapamycin profile matched the signature of GC sensitivity. We tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells and found that it sensitized to GC-induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis and that the combination of rapamycin and glucocorticoids has potential utility in lymphoid malignancies. Furthermore, this approach represents a strategy for identification of promising combination therapies for cancer.

Animals↗
PubMed2006

Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse.

The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human prostate xenograft CWR22. Here, we report that Etk is up-regulated in human prostate tumor specimens surveyed. Knocking down Etk expression by a specific small interfering RNA (siRNA) in prostate cancer cells attenuates cell proliferation, suggesting an essential role of Etk for prostate cancer cell survival and growth. Targeted expression of Etk in mouse prostate epithelium results in pathologic changes resembling human prostatic intraepithelial neoplasia, indicating that up-regulation of Etk may contribute to prostate cancer development. A marked increase of luminal epithelial cell proliferation was observed in the Etk transgenic prostate, which may be attributed in part to the elevated activity of Akt and signal transducers and activators of transcription 3 (STAT3). More interestingly, the expression level of acetyltransferase cyclic AMP-responsive element binding protein-binding protein (CBP) is also increased in the Etk transgenic prostate as well as in a prostate cancer cell line overexpressing Etk, concomitant with elevated histone 3 acetylation at lysine 18 (H3K18Ac). Down-modulation of Etk expression by a specific siRNA leads to a decrease of H3 acetylation in prostate cancer cell lines. Our data suggest that Etk may also modulate chromatin remodeling by regulating the activity of acetyltransferases, such as CBP. Given that Etk may exert its effects in prostate through modulation of multiple signaling pathways altered in human prostate cancer, the Etk transgenic mouse model may be a useful tool for studying the functions of Etk and identification of new molecular markers and drug targets relevant to human diseases.

Animals↗
PubMed2006

Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and the risk of endometriosis and adenomyosis in China.

Matrix metalloproteinases (MMPs) may contribute to the development of endometriosis. The aim of this study was to assess the effects of the polymorphisms in the promoters of MMP-7 (181A/G) and MMP-9 (1562C/T) on the risk of occurrence of endometriosis and adenomyosis. We genotyped 219 patients (143 women with endometriosis, 76 women with adenomyosis) and 160 control women in North China. There was a significant difference in frequency of the MMP-7 genotype between endometriosis and controls (P = 0.01) and also between adenomyosis and controls (P = 0.01). The frequency of the G allele in two groups of patients (7.3 and 7.9%) was significantly higher than in the controls (2.8%) (P = 0.01 and 0.01, respectively). Compared to the A/A genotype, the genotype with the -181G allele showed a significantly increased susceptibility to both diseases, with adjusted odds ratio of 2.62 [95% confidence interval (CI) = 1.17-5.87] for endometriosis and 3.14 (95% CI = 1.26-7.81) for adenomyosis. However, the overall genotype and allelotype distribution of the MMP-9 in the two case groups were not different from that of controls. We conclude that MMP-7-181A/G polymorphism has a potential to be a susceptibility factor for endometriosis and adenomyosis while MMP-9-1562C/T polymorphism may not provide a useful marker to predict susceptibility to endometriosis and adenomyosis, at least in women from North China.

Adult↗
PubMed2006

Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members.

We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival.

Amino Acid Sequence↗
PubMed2005

Lipopolysaccharide-induced production of interleukin-10 is promoted by the serine/threonine kinase Akt.

The bacterial endotoxin lipopolysaccharide (LPS), is a potent inducer of the inflammatory response. Previous studies demonstrated that LPS-induced toxicity is reversed upon FcgammaR clustering by IgG immune complexes (IC) through upregulation of the anti-inflammatory cytokine IL-10. The PI3K-Akt pathway is also reported to reverse LPS-induced inflammation. In this study, we have examined the role of Akt in LPS-induced IL-10 production. First, we compared Akt activation in macrophages stimulated with either LPS alone, or with a combination of LPS and ICs. Our experiments revealed that while Akt was activated under both conditions, the level of activation was significantly higher in cells stimulated with LPS and ICs, suggesting that Akt may be involved in IC-induced upregulation of IL-10 production. Using several independent models we have then tested the notion that enhanced Akt activation may lead to enhanced LPS-induced IL-10 production. Over-expression of constitutively active Myr-Akt in the mouse macrophage cell line Raw 264.7 led to significant increase in IL-10 production in response to LPS. In addition, down-regulation of Akt by siRNA resulted in a decrease in LPS-induced IL-10 production. Peritoneal macrophages from transgenic mice with macrophage-specific expression of Myr-Akt produced significantly higher levels of IL-10 when stimulated with LPS, compared to their wild-type counterparts. Consistent with this observation, serum levels of IL-10, post-LPS challenge, was higher in the Myr-Akt transgenic mice compared to the wild-type mice. Taken together, these data demonstrate that Akt plays a critical role in LPS-induced production of IL-10.

Animals↗
PubMed2005

The function of the SNP in the MMP1 and MMP3 promoter in susceptibility to endometriosis in China.

Matrix metalloproteinases (MMPs) may contribute to the development of endometriosis. Genetic variations in several MMP promoters may influence the transcription and expression of MMPs. The purpose of the present study was to assess how gene polymorphisms in the MMP1 and MMP3 promoters affect the risk of development of endometriosis. We genotyped 100 women with endometriosis and 150 control subjects in North China. There was a significant difference in frequency of the MMP1 genotype between cases and controls (P=0.03). The 2G homozygote in endometriosis and controls was significantly different (P=0.02). The frequency of the 2G allele among affected women (79%) was significantly higher than among the healthy controls (66.9%; P=0.003). However, the overall genotype and allelotype distribution of the MMP3 single nucleotide polymorphism (SNP) in patients was not different from that of controls (P> or =0.05). MMP1 and MMP3 polymorphisms were in linkage disequilibrium in cases and controls (D'=0.47; P=0.00). The haplotype frequency distribution derived from these two polymorphisms was significantly different between cases and controls (P=0.00). The haplotype analysis suggested an implication of both MMP1 and MMP3 polymorphisms in the susceptibility to endometriosis. We conclude that the MMP1 promoter SNP and MMP 2G/6A haplotype may modify susceptibility to endometriosis, but that the MMP3 promoter SNP is unlikely to be associated with endometriosis in the population of North China.

Adult↗
PubMed2005

[Efficacy of intraoperative hypotonic peritoneal chemo-hyperthermia combined with early postoperative intraperitoneal chemotherapy on gastric cancer].

BACKGROUND & OBJECTIVE: Abdominal recurrence from exfoliated cancer cells contributes a lot to treatment failure of advanced gastric cancer. Intraperitoneal chemotherapy, which has been proved effective in eliminating exfoliated cancer cells in abdominal cavity, is a hot topic on treatment of gastric cancer. This study was to explore application of combined therapy of intraoperative hypotonic peritoneal chemo-hyperthermia and early postoperative intraperitoneal chemotherapy to gastric cancer. METHODS: A total of 156 gastric cancer patients were randomized into 3 groups, and underwent the combined therapy (treatment group 1), intraoperative chemotherapy (treatment group 2), and peritoneal lavage with distilled water (control group), respectively. RESULTS: The 2-year survival rate of treatment group 1 was significantly higher than that of control group (88.4% vs. 65.2%, P < 0.05). The 3-year survival rate of treatment group 1 was significantly higher than those of treatment group 2, and control group (71.1% vs. 50.0%, and 45.6%, P < 0.05). Occurrence of liver metastasis was significantly lower in treatment groups 1 and 2 than in control group (7.7%, and 10.2% vs. 27.3%, P < 0.05). CONCLUSIONS: Combined therapy of intraoperative hypotonic chemo-hyperthermia and early postoperative intraperitoneal chemotherapy is effective for gastric cancer. Intraperitoneal chemotherapy can be used to prevent postoperative liver metastasis of gastric cancer.

Adult↗
PubMed2005

[Experimental study on the antagonistic activity of cationic multi-peptide mastoparan-1 against lipopolysaccharide].

OBJECTIVE: To explore the mechanism of cationic multi-peptide mastoparan-1 (MP-1) on the protection of mice from lipopolysaccharide (LPS) challenge. METHODS: Thirty Kunming mice were divided randomly into MP-1, injury, protection groups with 10 mice in each group. The mice in MP-1 group were injected with 3 mg/kg MP-1 by tail vein, while those in injury group were injected with 20 mg/kg LPS by tail vein, and those in protection group 3 mg/kg MP-1 within 20 seconds after 20 mg/kg LPS injection were injected. The effects of MP-1 on the protection of mice from LPS challenge were observed. In vitro, the affinity of MP-1 and PMB to LPS was compared by biosensor and FAST fit construct and expressed as Kd. And the neutralizing activity of MP-1 and PMB in dose of 5, 10, 20, 40 micromol/L on LPS (2 microg/L) was detected by dynamic turbidimetric limulus test with LPS neutralizing 0 micromol/L MP-1 and PMB as control. The mRNA expression levels of TLR4, TNF-alpha and IL-6 in murine peritoneal macrophages (PM phi) after exposure to LPS (100 ng/ml) were assayed by RT-PCR. RESULTS: MP-1 could significantly protect mice from LPS challenging with protection rate of 90%. In vitro, MP-1 had a high affinity (Kd value: 484.0 nmol/L) and neutralizing ability with LPS, but it was lower than that of PMB (Kd value: 18.9 nmol/L). The neutralizing effect of 20 and 40 micromol/L MP-1 was obviously stronger than that in 0 micromol/L (P < 0.01). MP could obviously inhibit the expression of TLR4, TNF-alpha and IL-6 mRNA in LPS-stimulated murine PM phi. CONCLUSION: MP-1 can evidently protect mice from lethal LPS challenge, and the mechanism might be related to the activity of MP-1 which binding and neutralizing LPS, blocking the combination LPS with its receptors. So the murine macrophage activation induced by LPS was inhibited.

Animals↗
PubMed2005

[Study of the anti-endotoxin effect of beta-1, 2, 3, 4, 6-penta-O-galloyl-D-glucopyranose in vitro].

OBJECTIVE: To study the anti-endotoxin effect of beta-1, 2, 3, 4, 6-penta-O-galloyl-D-glucopyranose (PGG) in vitro. METHODS: The affinity of PGG with lipid A was determined with biosensor technology, and the endotoxin-neutralizing effect was assayed with LAL. Human peripheral blood mononuclear cells (hPBMC) were separated from healthy donors and cultured in vitro. The effect of different concentrations of PGG on the release of TNF-alpha and hIL-6 from LPS-stimulated hPBMC were measured by ELISA method. RESULTS: Lipid A was combined with different concentrations of PGG. The combination speed was shortened with the increase in PGG concentration. The KD value between PGG and Lipid A was 5.2 x 10(-7) mol/L. The release of TNF-alpha and IL-6 of hPBMC under LPS stimulation (958 +/- 234 ng/L vs 1 351 +/- 99 ng/L) was obviously inhibited by PGG in the concentration of higher than 20 mg/L compared with that without PGG treatment (1 788 +/- 171 ng/L vs 1 965 +/- 232 ng/L, P < 0.05). CONCLUSION: PGG show an anti-endotoxin effect in vitro, which may be associated with its ability to combine and neutralize endotoxin.

Biosensing Techniques↗
PubMed2004

The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.

3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration.

Animals↗
PubMed2004

The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis in murine macrophages through the activation of p70S6 kinase.

Fc gamma receptor (Fc gamma R) clustering by immune complexes activates multiple signaling pathways leading to phagocytosis. We and others have previously reported that Akt is phosphorylated in response to Fc gamma R clustering. However, the functional consequence of Akt activation by Fc gamma R is not known. Using Raw 264.7 macrophage cells transfected to overexpress either constitutively active myristoylated (Myr)-Akt or a dominant-negative CAAX-Akt and bone marrow macrophages (BMMs) from wild-type and transgenic mice expressing macrophage-specific Myr-Akt, we analyzed the function of Akt in phagocytosis. We report that overexpression of Myr-Akt resulted in significant increase in phagocytic efficiency, whereas CAAX-Akt down-regulated phagocytosis in Raw 264.7 cells. Likewise BMMs expressing Myr-Akt displayed enhanced phagocytic ability. Analyzing the downstream effectors of Akt, we demonstrate that p70S6 kinase is constitutively phosphorylated in Myr-Akt-expressing BMMs. p70S6 kinase is reported to influence actin cytoskeleton and cell migration, suggesting that Akt may influence phagocytosis through the activation of p70S6 kinase. Consistent with this, overexpression of either wild-type or constitutively active but not a kinase-inactive p70S6 kinase in Raw 264.7 cells significantly enhanced phagocytosis. Likewise suppression of p70S6 kinase with rapamycin down-regulated phagocytic efficiency conferred by the expression of constitutively active Akt. These findings demonstrate a novel role for Akt in phagocytosis through the activation of p70S6 kinase.

Animals↗
PubMed2004

Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model.

The Ets2 transcription factor is constitutively phosphorylated on residue Thr(72) in macrophages derived from mice homozygous for the motheaten viable (me-v) allele of the hemopoietic cell phosphatase (Hcph) gene. To genetically test the importance of signaling through residue Thr(72) of Ets2 during inflammation, the Ets2(A72) mutant allele, which cannot be phosphorylated on Thr(72), was combined with the Hcph(me-v) allele in mice. Ets2(A72/A72) moderated the inflammation-related pathology of Hcph(me-v/me-v) mice, as demonstrated by the increased life span and the decreased macrophage infiltration in skin and lungs of these mice. Macrophage apoptosis induced by cytokine withdrawal was also increased in the double-mutant mice. Importantly, the Ets2(A72/A72) allele resulted in decreased expression of inflammatory response genes, including TNF-alpha, CCL3, matrix metalloprotease 9, integrin alpha(M), and Bcl-X in alveolar macrophage. Ets2 phosphorylation was required for persistent activation of TNF-alpha following LPS stimulation of bone marrow-derived macrophages. The phosphorylation of Ets2 functions in the severe inflammatory phenotype of the me-v model by mediating both macrophage survival and inflammatory gene expression.

Animals↗
PubMed2004

The inositol 3-phosphatase PTEN negatively regulates Fc gamma receptor signaling, but supports Toll-like receptor 4 signaling in murine peritoneal macrophages.

Fc gamma R clustering in macrophages activates signaling events that result in phagocytosis. Phagocytosis is accompanied by the generation harmful byproducts such as reactive oxygen radicals and production of inflammatory cytokines, which mandate that the phagocytic process be subject to a tight regulation. The molecular mechanisms involved in this regulation are not fully understood. In this study, we have examined the role of the inositol 3-phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in Fc gamma R-induced macrophage function. We demonstrate that in ex vivo murine peritoneal macrophages that are deficient in PTEN expression, Fc gamma R-induced Akt and extracellular signal-regulated kinase phosphorylation are enhanced. Notably, PTEN(-/-) macrophages showed constitutively high phosphorylation of Akt. However, PTEN did not seem to influence tyrosine phosphorylation events induced by Fc gamma R clustering. Furthermore, PTEN(-/-) macrophages displayed enhanced phagocytic ability. Likewise, Fc gamma R-induced production of TNF-alpha, IL-6, and IL-10 was significantly elevated in PTEN(-/-) macrophages. Surprisingly, LPS-induced TNF-alpha production was down-regulated in PTEN(-/-) macrophages. Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN(-/-) cells. Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. Our observation that Akt activation is basally enhanced in PTEN(-/-) cells suggests that PTEN supports TLR4-induced inflammatory responses by suppressing the activation of Akt. Thus, we conclude that PTEN is a negative regulator of Fc gamma R signaling, but a positive regulator of TLR4 signaling. These findings are the first to demonstrate a role for PTEN in Fc gamma R- and TLR4-mediated macrophage inflammatory response.

Animals↗