Induction of proinflammatory mediators requires activation of the TRAF, NIK, IKK and NF-κB signal transduction pathway in astrocytes infected with<i>Escherichia coli</i>

Kim, J. M.; Oh, Yu‐Kyoung; Lee, J. H.; Im, Dong-Su; Kim, Y.-J.; Youn, Jeehee; Lee, C.-H.; Son, Hyeon; Lee, Y.-S.; Park, J. Y.; Choi, In Hong

doi:10.1111/j.1365-2249.2005.02804.x

Cited by 38 publications

(30 citation statements)

References 52 publications

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“…Neuroinflammation is a hallmark of various CNS pathologies such as trauma, bacterial meningitis, brain abscess, Alzheimer's disease, and multiple sclerosis, which share a general feature of reactive gliosis characterized, to varying degrees, by the proliferation and hypertrophy of activated astrocytes (Eikelenboom et al, 2002;Griffin and Mrak, 2002;Kielian, 2004;Koedel et al, 2002;McGeer and McGeer, 2002;Nau and Bruck, 2002;Scheld et al, 2002). When activated by an appropriate stimulus, astrocytes have the capacity to produce robust amounts of proinflammatory mediators which may have profound effects on GJC (Dong and Benveniste, 2001;Esen et al, 2004;Kim et al, 2005;Smits et al, 2001). Indeed, the gram-negative bacterial cell wall component lipopolysaccharide (LPS) has been shown to attenuate GJC in primary rat astrocytes, which was attributed, in part, to the autocrine/paracrine action of nitric oxide (NO), since the iNOS inhibitor N G -monoethyl-L-arginine (NMMA) was capable of restoring gap junction coupling (Bolanos and Medina, 1996).…”

Section: Introductionmentioning

confidence: 99%

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

Esen

Shuffield

Syed

et al. 2006

Glia

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Gap junctions establish direct intercellular conduits between adjacent cells and are formed by the hexameric organization of protein subunits called connexins (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS infection with S. aureus, one of the main etiologic agents of brain abscess in humans, is capable of eliciting regional changes in astrocyte homocellular gap junction communication (GJC) and, by extension, influencing neuron homeostasis at sites distant from the primary focus of infection. Here we investigated the effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30, and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however, Cx26 levels were elevated following bacterial exposure. Functional examination of dye coupling, as revealed by single-cell microinjections of Lucifer yellow, demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be regulated by a factor(s) that requires de novo protein production; however, CHX did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK inhibitor SB202190 was capable of partially restoring the S. aureus-mediated decrease in astrocyte GJC to that of unstimulated cells, suggesting the involvement of p38 MAPK-dependent pathway(s). These findings could have important implications for limiting the long-term detrimental effects of abscess formation in the brain which may include seizures and cognitive deficits.

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Section: Introductionmentioning

confidence: 99%

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

Esen

Shuffield

Syed

et al. 2006

Glia

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“…These cells support metabolic functions of neurons and maintain CNS homeostasis but they also have immune functions in the CNS. Stimuli such as A␤, Escherichia coli, Poly I:C, LPS, and Flagellin induce production of chemokines such as CCL2 and CXCL1 in astrocytes in vitro (Kim et al, 2005;McKimmie and Graham, 2010) and both TNF-␣ and IL-1␤ can also induce astrocyte CCL2 and CXCL1 in vitro (Thompson and Van Eldik, 2009;An et al, 2011;Choi et al, 2011;Lee et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines IL-1β and TNF-α

2015

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Microgliosis and astrogliosis are standard pathological features of neurodegenerative disease. Microglia are primed by chronic neurodegeneration such that toll-like receptor agonists, such as LPS, drive exaggerated cytokine responses on this background. However, sterile inflammatory insults are more common than direct CNS infection in the degenerating brain and these insults drive robust IL-1␤ and TNF-␣ responses. It is unclear whether these pro-inflammatory cytokines can directly induce exaggerated responses in the degenerating brain. We hypothesized that glial cells in the hippocampus of animals with chronic neurodegenerative disease (ME7 prion disease) would display exaggerated responses to central cytokine challenges. TNF-␣ or IL-1␤ were administered intrahippocampally to ME7-inoculated mice and normal brain homogenate-injected (NBH) controls. Both IL-1␤ and TNF-␣ produced much more robust IL-1␤ synthesis in ME7 than in NBH animals and this occurred exclusively in microglia. However, there was strong nuclear localization of the NFB subunit p65 in the astrocyte population, associated with marked astrocytic synthesis of the chemokines CXCL1 and CCL2 in response to both cytokine challenges in ME7 animals. Conversely, very limited expression of these chemokines was apparent in NBH animals similarly challenged. Thus, astrocytes are primed in the degenerating brain to produce exaggerated chemokine responses to acute stimulation with pro-inflammatory cytokines. Furthermore, this results in markedly increased neutrophil, T-cell, and monocyte infiltration in the diseased brain. These data have significant implications for acute sterile inflammatory insults such as stroke and traumatic brain injury occurring on a background of aging or neurodegeneration.

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“…Receptor signaling that activates transcription factors such as NF-B and STAT regulate transcription of many inflammatory mediators, including cytokines and chemokines (13)(14)(15)(16). NF-B signaling is activated in response to CNS injury (17)(18)(19).…”

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confidence: 99%

NF-κB-Driven STAT2 and CCL2 Expression in Astrocytes in Response to Brain Injury

Khorooshi

Babcock

Owens

2008

The Journal of Immunology

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Tissue response to injury includes expression of genes encoding cytokines and chemokines. These regulate entry of immune cells to the injured tissue. The synthesis of many cytokines and chemokines involves NF-κB and signal transducers and activators of transcription (STAT). Injury to the CNS induces glial response. Astrocytes are the major glial population in the CNS. We examined expression of STATs and the chemokine CCL2 and their relationship to astroglial NF-κB signaling in the CNS following axonal transection. Double labeling with Mac-1/CD11b and glial fibrillary acidic protein revealed that STAT2 up-regulation and phosphorylation colocalized exclusively to astrocytes, suggesting the involvement of STAT2 activating signals selectively in astroglial response to injury. STAT1 was also up-regulated and phosphorylated but not exclusively in astrocytes. Both STAT2 up-regulation and phosphorylation were NF-κB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-κB activation in astrocytes. We further showed that lack of NF-κB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte infiltration. Our results suggest that NF-κB signaling in astrocytes controls expression of both STAT2 and CCL2, and thus regulates infiltration of leukocytes into lesion-reactive hippocampus after axonal injury. Taken together, these findings indicate a central role for astrocytes in directing immune-glial interaction in the CNS injury response.

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Induction of proinflammatory mediators requires activation of the TRAF, NIK, IKK and NF-κB signal transduction pathway in astrocytes infected withEscherichia coli

Abstract: SummaryEscherichia coli is associated with inflammation in the brain. To investigate whether astrocytes are involved in E. coil -induced inflammation, we assessed the levels of expression of proinflammatory mediators produced by E. coliinfected astrocytes.

Cited by 38 publications

References 52 publications

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus

Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines IL-1β and TNF-α

NF-κB-Driven STAT2 and CCL2 Expression in Astrocytes in Response to Brain Injury

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