ArticleMolecular systems biology2024
Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.
Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Dissection of MAPK and NF-κB p65 signaling dynamics underlying LPS tolerance in macrophages at the single-cell level.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Macrophage response specificity to ligand mixtures is improved by signaling pathway antagonism.Molecular systems biology · 2026Article
- Exploring the Distinct Regulatory Actions and Molecular Pathways of Coptisine Through Network Pharmacology: Insights Into Its Influence on Platelet Activation and Thrombus Development.Food science & nutrition · 2026Article
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- Research progress on the mechanisms of Panax ginseng and its active components in maintaining skin homeostasis and disease intervention.Chinese medicine · 2026Review
- The Putative RNA Methyltransferase Modulates T3SS Expression and Host NF-κB Activation via T6SS-Mediated Translocation inInternational journal of molecular sciences · 2026Article
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- Exploring the Mechanism of Bu Zhong Yi Qi Decoction in Treating Sepsis-induced Acute Lung Injury based on Network Pharmacology and Experimental Verification.Current pharmaceutical design · 2026Article
- Aspergillus fumigatus Gliotoxin Inhibits LC3-Associated Phagocytosis in Macrophages in a Calcium-Dependent Manner.Journal of immunology research · 2026Article
- Agent-specific training directs distinctive immune response againstFrontiers in immunology · 2026Article
- Reconstructing noisy gene regulation dynamics using extrinsic-noise-driven neural stochastic differential equations.PLoS computational biology · 2025Article
- A computational workflow for assessing drug effects on temporal signaling dynamics reveals robustness in stimulus-specific NFκB signaling.PLoS computational biology · 2025Article
- Regulating inflammation microenvironment and tenogenic differentiation as sequential therapy promotes tendon healing in diabetic rats.Journal of orthopaedic translation · 2025Article
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- The immune microenvironment in endometrial carcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2025Review
- Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
10 authors.
Funding
Abstract
Macrophages sense pathogens and orchestrate specific immune responses. Stimulus specificity is thought to be achieved through combinatorial and dynamical coding by signaling pathways. While NFκB dynamics are known to encode stimulus information, dynamical coding in other signaling pathways and their combinatorial coordination remain unclear. Here, we established live-cell microscopy to investigate how NFκB and p38 dynamics interface in stimulated macrophages. Information theory and machine learning revealed that p38 dynamics distinguish cytokine TNF from pathogen-associated molecular patterns and high doses from low, but contributed little to information-rich NFκB dynamics when both pathways are considered. This suggests that immune response genes benefit from decoding immune signaling dynamics or combinatorics, but not both. We found that the heterogeneity of the two pathways is surprisingly uncorrelated. Mathematical modeling revealed potential sources of uncorrelated heterogeneity in the branched pathway network topology and predicted it to drive gene expression variability. Indeed, genes dependent on both p38 and NFκB showed high scRNAseq variability and bimodality. These results identify combinatorial signaling as a mechanism to restrict NFκB-AND-p38-responsive inflammatory cytokine expression to few cells.
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