Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide‐injected brain

Ji, Kyung-Ae; Yang, Myung-Soon; Jeong, Hey-Kyeong; Min, Kyoung‐jin; Kang, Shin-Wook; Jou, Ilo; Joe, Eun‐Hye

doi:10.1002/glia.20571

Cited by 106 publications

(161 citation statements)

References 42 publications

Supporting

Mentioning

144

Contrasting

Order By: Relevance

“…In PBS-treated control animals, ionized calcium binding adaptor molecule 1-immunopositive (Iba-1 + ) microglia showed a ramified morphology ( Figure 1A). Microglial cell density in the substantia nigra reticulate (SNr), where dopaminergic neuronal processes are located, was higher than that in the SNpc, as previously reported (Ji et al, 2007). The processes of Iba-1 + microglia became slightly shorter and thicker 8 h after iv LPS injection, and these features were more prominent in the SNpc than in the SNr.…”

Section: Behavior Of Microglia and Astrocytes In Response To Systemicsupporting

confidence: 74%

“…Neutrophils are recruited to LPS-injected, traumatic, and ischemic brains, and the inflammatory responses are neurotoxic (Ji et al, 2007;Matsumoto et al, 2007). Thus, we examined the neutrophil infiltration pattern of the brain in response to iv LPS injection.…”

Section: Neutrophils Infiltrate the Brain In Response To Systemic Admmentioning

confidence: 99%

“…However, it is not clear whether systemic inflammation induces a level of brain inflammation sufficiently intense to cause neuronal damage. Cultured microglia challenged with LPS and interferon-γ produce neurotoxic inflammatory mediators including inducible nitric oxide synthase (iNOS) (Liu et al, 2000;Possel et al, 2000;Min et al, 2006), whereas microglia activated in vivo by brain injury and/or LPS injection synthesize very little iNOS and are not neurotoxic (Ji et al, 2007;Matsumoto et al, 2007). In the present study, we investigated how systemic inflammation affected brain inflammation, and whether such inflammation caused neuronal toxicity.…”

mentioning

confidence: 90%

See 2 more Smart Citations

Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

2010

Self Cite

View full text Add to dashboard Cite

It has been suggested that brain inflammation is important in aggravation of brain damage and/or that inflammation causes neurodegenerative diseases including Parkinson's disease (PD). Recently, systemic inflammation has also emerged as a risk factor for PD. In the present study, we evaluated how systemic inflammation induced by intravenous (iv) lipopolysaccharides (LPS) injection affected brain inflammation and neuronal damage in the rat. Interestingly, almost all brain inflammatory responses, including morphological activation of microglia, neutrophil infiltration, and mRNA/protein expression of inflammatory mediators, appeared within 4-8 h, and subsided within 1-3 days, in the substantia nigra (SN), where dopaminergic neurons are located. More importantly, however, dopaminergic neuronal loss was not detectable for up to 8 d after iv LPS injection. Together, these results indicate that acute induction of systemic inflammation causes brain inflammation, but this is not sufficiently toxic to induce neuronal injury.

show abstract

Section: Behavior Of Microglia and Astrocytes In Response To Systemicsupporting

confidence: 74%

Section: Neutrophils Infiltrate the Brain In Response To Systemic Admmentioning

confidence: 99%

mentioning

confidence: 90%

See 1 more Smart Citation

Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…We also confirmed these results by confocal microscopy. Iba-1 has been described previously to be specific for microglial cells [43,44]. Figure 2C shows that Iba-1-positive microglia expressed BAFF in resting and Gmix-stimulated conditions.…”

Section: Gmix Stimulates Microglia To Express Baff In Doseand Time-desupporting

confidence: 51%

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Kim

Park

Jou

et al. 2009

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

BAFF is a recently identified member of the TNF ligand superfamily that plays a critical role in B cell differentiation, survival, and regulation of Ig production. In the present study, we examined whether BAFF is expressed in microglia, and the expression and release of BAFF are regulated by gangliosides. The results showed that BAFF was expressed and released in rat primary microglia as well as in BV-2 cells. Furthermore, its expression and release were increased by gangliosides stimulation and regulated by JAK-STAT, especially the STAT1-and STAT3-dependent signaling pathways. It was of particular interest to observe that SP600125 and SB203580, specific inhibitors of JNK and p38, did not inhibit BAFF synthesis but inhibited the release of sBAFF in gangliosides-treated cells by regulating furin expression, suggesting that the JNK and p38 signaling pathways regulate the release but not the synthesis of BAFF. Moreover, BV-2 cells expressed BAFF-R on their cell surface, and rat primary microglia expressed BAFF-R and TACI on their cell surface. rBAFF increased the release of cytokines, especially IL-6, TNF-␣, and IL-10, in rat primary microglia as well as in BV-2 cells. These findings imply that BAFF secreted by microglia may play important roles in CNS inflammation by regulating microglia as well as infiltrated B cells.

show abstract

“…Next, we analyzed EP2 and EP4 receptor expression in spinal sections of naïve and LPS-primed mice. CD11b costaining allowed the identification of microglia and/or macrophages, whose invasion into the spinal cord can also be induced by LPS (33). Upon LPS priming, amoeboid-shaped cells with strong CD11b staining appeared in the spinal cord.…”

Section: Lps Priming Induces Ep2 and Ep4 Expression In Spinal Microglmentioning

confidence: 99%

Anti-inflammatory Role of Microsomal Prostaglandin E Synthase-1 in a Model of Neuroinflammation

Brenneis

Coste

Altenrath

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

A major immunological response during neuroinflammation is the activation of microglia, which subsequently release proinflammatory mediators such as prostaglandin E 2 (PGE 2 ). Besides its proinflammatory properties, cyclooxygenase-2 (COX-2)-derived PGE 2 has been shown to exhibit anti-inflammatory effects on innate immune responses. Here, we investigated the role of microsomal PGE 2 synthase-1 (mPGES-1), which is functionally coupled to COX-2, in immune responses using a model of lipopolysaccharide (LPS)-induced spinal neuroinflammation. Interestingly, we found that activation of Eprostanoid (EP)2 and EP4 receptors, but not EP1, EP3, PGI 2 receptor (IP), thromboxane A 2 receptor (TP), PGD 2 receptor (DP), and PGF 2 receptor (FP), efficiently blocked LPS-induced tumor necrosis factor ␣ (TNF␣) synthesis and COX-2 and mPGES-1 induction as well as prostaglandin synthesis in spinal cultures. In vivo, spinal EP2 receptors were up-regulated in microglia in response to intrathecally injected LPS. Accordingly, LPS priming reduced spinal synthesis of TNF␣, interleukin 1␤ (IL-1␤), and prostaglandins in response to a second intrathecal LPS injection. Importantly, this reduction was only seen in wild-type but not in mPGES-1-deficient mice. Furthermore, intrathecal application of EP2 and EP4 agonists as well as genetic deletion of EP2 significantly reduced spinal TNF␣ and IL-1␤ synthesis in mPGES-1 knock-out mice after LPS priming. These data suggest that initial inflammation prepares the spinal cord for a negative feedback regulation by mPGES-1-derived PGE 2 followed by EP2 activation, which limits the synthesis of inflammatory mediators during chronic inflammation. Thus, our data suggest a role of mPGES-1-derived PGE 2 in resolution of neuroinflammation.Neurodegenerative disorders, including Alzheimer and Parkinson disease, multiple sclerosis, and spinal cord or peripheral nerve injury, are associated with neuroinflammation (1, 2). Its initiation, maintenance and resolution are regulated by various cell types, including resident microglia, astroglia, and oligodendrocytes as well as invading blood leukocytes. Lipopolysaccharide (LPS) has traditionally been used to simulate innate immune responses in the central nervous system (CNS) by activating toll-like receptor-4 of microglia (3). Upon activation, microglia release inflammatory mediators such as cytokines, chemokines, free radicals, nitric oxide, or prostaglandins (4). One of the earliest events during LPS-induced neuroinflammation is the synthesis and release of the proinflammatory cytokine TNF␣ by microglia, which reaches maximum concentrations 2-8 h after the initial inflammatory stimulus (5). In effector cells, TNF␣ induces the expression of multiple proteins that further enhance the inflammatory response, including cyclooxygenase-2 (COX-2) and the functionally coupled microsomal PGE 2 synthase-1 (mPGES-1) 2 (6, 7). After 24 h, TNF␣ levels decrease to base-line levels whereas the activation of glia persists for several days (8). The mechanisms controlling the precise...

show abstract

Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide‐injected brain

Cited by 106 publications

References 42 publications

Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Anti-inflammatory Role of Microsomal Prostaglandin E Synthase-1 in a Model of Neuroinflammation

Contact Info

Product

Resources

About