ArticleFree radical biology & medicine2015
MKK3 mediates inflammatory response through modulation of mitochondrial function.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- Nicotinamide mononucleotide ameliorates acute lung injury by inducing mitonuclear protein imbalance and activating the UPRExperimental biology and medicine (Maywood, N.J.) · 2022Article
- Standardized fraction of Xylocarpus moluccensis inhibits inflammation by modulating MAPK-NFκB and ROS-HIF1α-PKM2 activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Integrative multiplatform-based molecular profiling of human colorectal cancer reveals proteogenomic alterations underlying mitochondrial inactivation.American journal of cancer research · 2021Article
- Pharmacological validation of targets regulating CD14 during macrophage differentiation.EBioMedicine · 2020Article
- Roles of Phenolic Compounds in the Reduction of Risk Factors of Cardiovascular Diseases.Molecules (Basel, Switzerland) · 2019Review
- The Role of Mitophagy in Innate Immunity.Frontiers in immunology · 2018Review
- Proteomics data on MAP Kinase Kinase 3 knock out bone marrow derived macrophages exposed to cigarette smoke extract.Data in brief · 2017Article
- Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis.The Journal of infectious diseases · 2017Article
- Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD.The international journal of biochemistry & cell biology · 2016Review
- SILAC based protein profiling data of MKK3 knockout mouse embryonic fibroblasts.Data in brief · 2016Article
- Warburg revisited: lessons for innate immunity and sepsis.Frontiers in physiology · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondria are increasingly recognized as drivers of inflammatory responses. MAP kinase kinase 3 (MKK3), a dual-specificity protein kinase, is activated in inflammation and in turn activates p38 MAP kinase signaling. Here we show that MKK3 influences mitochondrial function and acts as a critical mediator of inflammation. MKK3-deficient (MKK3(-/-)) mice and bone marrow-derived macrophages (BMDMs) secreted smaller amounts of cytokines than wild type (WT) after lipopolysaccharide (LPS) exposure. There was improved mitochondrial function, as measured by basal oxygen consumption rate, mitochondrial membrane potential, and ATP production, in MKK3(-/-) BMDMs. After LPS exposure, MKK3(-/-) BMDMs did not show a significant increase in cellular reactive oxygen species production or in mitochondrial superoxide compared to WT. Activation of two important inflammatory mediators, i.e., the nuclear translocation of NF-κB and caspase-1 activity (a key component of the inflammasome), was lower in MKK3(-/-) BMDMs. p38 and JNK activation was lower in MKK3(-/-) BMDMs compared to WT after exposure to LPS. Knockdown of MKK3 by siRNA in wild-type BMDMs improved mitochondrial membrane potential, reduced LPS-induced caspase-1 activation, and attenuated cytokine secretion. Our studies establish MKK3 as a regulator of mitochondrial function and inflammatory responses to LPS and suggest that MKK3 may be a therapeutic target in inflammatory disorders such as sepsis.
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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.