The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Interactive role of the toll‐like receptor 4 and reactive oxygen species in LPS‐induced microglia activation
Abstract
Microglia are activated by lipopolysaccharide (LPS) to produce neurotoxic pro‐inflammatory factors and reactive oxygen species (ROS). While a multitude of LPS receptors and corresponding pathways have been identified, the detailed mechanisms mediating the microglial response to LPS are unclear. Using mice lacking a functional toll‐like receptor 4 (TLR4), we demonstrate that TLR4 and ROS work in concert to mediate microglia activation, where the contribution from each pathway is dependent on the concentration of LPS. Immunocytochemical staining of microglia in neuron–glia cultures with antibodies against F4/80 revealed that while TLR4+/+ microglia were activated the low concentration of 1 ng/ml of LPS, TLR4−/− microglia exhibit activated morphology in response to LPS only at higher concentrations (100–1,000 ng/ml). Additionally, tumor necrosis factor‐α (TNF‐α) was only produced from higher concentrations (100–1,000 ng/ml) of LPS in TLR4−/− enriched microglia cultures. Diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, reduced TNF‐α production from TLR4−/− microglia. The influence of TLR4 on LPS‐induced superoxide production was tested in rat enriched microglia cultures, where the presence or absence of serum failed to show any effect on the superoxide production. Further, both TLR4−/− and TLR4+/+ microglia showed a similar increase in extracellular superoxide production when exposed to LPS (1–1,000 ng/ml). These data indicate that LPS‐induced superoxide production in microglia is independent of TLR4 and that ROS derived from the production of extracellular superoxide in microglia mediates the LPS‐induced TNF‐α response of both the TLR4‐dependent and independent pathway. © 2005 Wiley‐Liss, Inc.
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Cites
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265
Self-citationLiu, B., & Hong, J.-S. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.035048 · Cited by 1,095
Self-citationLehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052
Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling
Forman, H. J., & Torres, M. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2206007 · Cited by 891 · cited 2×
“Activation of NADPH oxidase is known to increase intracellular ROS, which in turn enhances pro-inflammatory gene expression (Forman and Torres, 2002; Qin et al., 2004).”
BackgroundQin, L., Liu, Y., Wang, T., Wei, S.-J., Block, M. L., Wilson, B., Liu, B., & Hong, J.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307657200 · Cited by 574
Self-citationBrain microglia constitutively express β-2 integrins
Akiyama, H., & McGeer, P. L. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90055-r · Cited by 430
McGeer, P. L., Schwab, C., Parent, A., & Doudet, D. (2003) · Annals of Neurology · doi:10.1002/ana.10728 · Cited by 400
Chakravarty, S., & Herkenham, M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4268-04.2005 · Cited by 396
Liu, B., Du, L., & Hong, J.-S. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39275-4 · Cited by 347 · cited 1×
“Primary enriched microglia cultures were prepared from the whole brains of two-day-old rat or mouse pups, using the previously described procedure (Liu et al., 2000).”
MethodSelf-citationTan, A. S., & Berridge, M. V. (2000) · Journal of Immunological Methods · doi:10.1016/s0022-1759(00)00156-3 · Cited by 330
Cited by
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047
“Interestingly, unique to microglia, LPSinduced production of O2 ● is not mediated through the traditional LPS receptor, the toll-like 4 receptor.(50) In fact, recent work has indicated that the MAC-1 receptor is responsible for the LPS-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase a…”
BackgroundSelf-citationCD14 and Toll-Like Receptors 2 and 4 Are Required for Fibrillar Aβ-Stimulated Microglial Activation
Reed-Geaghan, E. G., Savage, J. C., Hise, A. G., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3158-09.2009 · Cited by 591
Microglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556
Role of Microglia TLRs in Neurodegeneration
Fiebich, B. L., Batista, C. R. A., Saliba, S. W., Yousif, N. M., & de Oliveira, A. C. P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00329 · Cited by 291
Metadata
- Authors
- Qin, L., Li, G., Qian, X., Liu, Y., Wu, X., Liu, B., Hong, J., & Block, M. L.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2005-05-26
- Volume
- 52
- Issue
- 1
- Pages
- 78-84
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2030539829
- Cited by
- 210
- References
- 10
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- closed
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