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Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation.
Glia. 2005 Oct; 52(1):78-84.GLIA

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-alpha (TNF-alpha) 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-alpha 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-alpha response of both the TLR4-dependent and independent pathway.

Authors+Show Affiliations

Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15920727

Citation

Qin, Liya, et al. "Interactive Role of the Toll-like Receptor 4 and Reactive Oxygen Species in LPS-induced Microglia Activation." Glia, vol. 52, no. 1, 2005, pp. 78-84.
Qin L, Li G, Qian X, et al. Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia. 2005;52(1):78-84.
Qin, L., Li, G., Qian, X., Liu, Y., Wu, X., Liu, B., Hong, J. S., & Block, M. L. (2005). Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia, 52(1), 78-84.
Qin L, et al. Interactive Role of the Toll-like Receptor 4 and Reactive Oxygen Species in LPS-induced Microglia Activation. Glia. 2005;52(1):78-84. PubMed PMID: 15920727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. AU - Qin,Liya, AU - Li,Guorong, AU - Qian,Xun, AU - Liu,Yuxin, AU - Wu,Xuefei, AU - Liu,Bin, AU - Hong,Jau-Shyong, AU - Block,Michelle L, PY - 2005/5/28/pubmed PY - 2006/8/10/medline PY - 2005/5/28/entrez SP - 78 EP - 84 JF - Glia JO - Glia VL - 52 IS - 1 N2 - 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-alpha (TNF-alpha) 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-alpha 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-alpha response of both the TLR4-dependent and independent pathway. SN - 0894-1491 UR - https://www.unboundmedicine.com/medline/citation/15920727/Interactive_role_of_the_toll_like_receptor_4_and_reactive_oxygen_species_in_LPS_induced_microglia_activation_ L2 - https://doi.org/10.1002/glia.20225 DB - PRIME DP - Unbound Medicine ER -