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Hypoxia Supports LPS-Driven Tolerance and Functional Activation in BV-2 Microglial Cells
by
, , , ,
Alicia Chavero Vargas
1
,
Natascha Köstlin-Gille
1,2,
Reinhard Bauer
3,
Stefanie Dietz-Ziegler
1,2,
Anita S. Lokaj
4,
Soumya Lutterbach
1,5,
Christian Gille
1 and
Trim Lajqi
1,*
1
Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
2
Department of Neonatology, University of Tübingen, 72076 Tübingen, Germany
3
Institute of Molecular Cell Biology, Jena University Hospital, 07745 Jena, Germany
4
Department of Ophthalmology, University Center Clinic of Kosovo, XK-10000 Prishtina, Kosovo
5
Department of Anesthesiology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Biology 2025, 14(11), 1512; https://doi.org/10.3390/biology14111512
Submission received: 24 September 2025
/
Revised: 23 October 2025
/
Accepted: 24 October 2025
/
Published: 28 October 2025
(This article belongs to the Section Immunology)
Simple Summary
This study explores the effects of short-term hypoxia on BV-2 microglial cells in vitro, focusing on inflammation, metabolism, and cellular functions. Our results show that hypoxia promotes a pronounced tolerant phenotype in BV-2 cells, characterized by reduced pro-inflammatory markers and decreased glycolytic activity via the MyD88/NF-κB p65 pathway. Tolerance acquisition enhances BV-2 microglial migration and phagocytosis via ERK1/2 signaling, but these effects are attenuated under hypoxic conditions. These findings provide new insights into hypoxia-driven modulation of tolerant microglia with potential implications for neuroinflammation and ischemic brain injury.
Abstract
(1) Background: Prolonged hypoxia contributes to irreversible organ damage, particularly in the brain and heart. While chronic hypoxia is harmful, mild short-term hypoxia can trigger protective mechanisms. This study investigates how such hypoxic conditions affect BV-2 tolerant microglial cells in vitro, focusing on inflammation, metabolism, and functional activity. Although in vitro models provide a controlled setting, our findings may offer insights into microglial behavior in vivo under similar conditions. (2) Methods: We used various molecular and biochemical techniques to assess the inflammatory state of BV-2 microglia under hypoxia, measuring glycolytic activity (via lactate production), and evaluating migratory and phagocytic capacities in vitro. (3) Results: Hypoxic conditions induced a more tolerant, anti-inflammatory phenotype in BV-2 cells, with decreased pro-inflammatory mediators and reduced glycolytic activity, regulated by the MyD88/NF-κB p65 pathway. Tolerance supports increased migration and phagocytosis, but under hypoxic conditions, these effects were significantly declined compared to normoxic conditions, mediated through the ERK1/2 pathway. (4) Conclusions: These findings suggest that short-term hypoxia may regulate microglial behavior and restore homeostasis, with implications for neuroinflammatory conditions.
Keywords:
microglia; tolerance; normoxia; hypoxia; inflammation; migration; phagocytosis
