Production of tumor necrosis factor-alpha by microglia and astrocytes in culture

Sawada, Makoto; Kondo, Noriaki; Suzumura, Akio; Marunouchi, Tohru

doi:10.1016/0006-8993(89)90078-4

Cited by 591 publications

(309 citation statements)

References 17 publications

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“…3 summarizes the influence of various effectors on the secretion of plasminogen. Lipopolysaeeharide, which is the most potent stimulant of IL.I [4], TNF [10], and NGF [6] secretion by microglia, increased the :iec~e-tion of plasminogen as reported previously [14]. Retinoic acid, one of the differentiation agents [17] for microglia [2], markedly promoted the plasminogen secre- tion by mieroglia.…”

Section: Determination Of Plasminogen In Miccmsupporting

confidence: 77%

“…To study these events, methods for isolation of microglia and an in vitro culture system have been developed [2][3][4][5]. So far, isolated and cultured microglia have been reported to produce the biologically active substances: nerve growth factor (1NGF) [6], interleukin-1 (1L-I) [7]~ IL-6 [8], tumor necrosis factor (TNF) [9,10] and basic fibroblast growth factor (bFGF) [11]. Furthermore, we recently found that microglia secrete some serine-type pretenses, which were identified as elasta~e [12] and a urokinase-type plasminogen activator fuPA) [13].…”

Section: Introductionmentioning

confidence: 99%

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Retinoic acid enhances the secretion of plasminogen from cultured rat microglia

Nakajima¹,

Takemoto²,

Kohsaka³

1992

FEBS Letters

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To determine the amount of plasmmogen in microghal condmoned medium, a highly sensitive and Sl~Clfic enzyme-linked immuno~orbent assay (ELISA) for lot plasmmogen wa~ e~tablished. Weak cross-reactwity with human serum plasminogen was observed, while no re.activity was deified with frog and carp plasmmogen. The specificity of the immuno~orbent a~say was confirmed by Western blotting. The secretion of plasmmogen into the microglial culture medium was ouantlfied by using the established ELISA and was found to be increased depending on the culture time and numbe~ of microgha The secretion was increased about 5-fold by stimulation with retmoic acid. while interleukm-1, and basic fibroblast growth factor showed no significant effect.Microgha; Plasmmogen, Enzyme-li!~ed immunosorbent assay, Culture; Conditioned medium 1, INTRODUCTIONMicroglia have been thought to be implicated not only in regeneration after injury or pathological damage but also in morphogenesis during development of the central nervous system (CNS) [1]. To study these events, methods for isolation of microglia and an in vitro culture system have been developed [2][3][4][5]. So far, isolated and cultured microglia have been reported to produce the biologically active substances: nerve growth factor (1NGF) [6], interleukin-1 (1L-I) [7]~ IL-6 [8], tumor necrosis factor (TNF) [9,10] and basic fibroblast growth factor (bFGF) [11]. Furthermore, we recently found that microglia secrete some serine-type pretenses, which were identified as elasta~e [12] and a urokinase-type plasminogen activator fuPA) [13]. More recently, plasminogen, which is a specific substrata of PA0 was also detected in microglial conditioned medium (Mic-CM) by zymography and Western blotting [14]. The de nero synthesis of plasminogen was also demonstrated in microglia [14]. However, how plasminogen secretion from microglia is regulated remained unknown. To obtain further information about microglia-derived plasminogen, we investigated the eflbct of retinoic acid° which is known to accelerate microglial differentiation [2], on the secretion of plasminogen from microglia. The effect of bFGF and iL-1, as stimulators of PA secretion by microglia [13], was also investigated. MATERIALS AND METHODS 1. Preparr.tton of mtc,oghtt! conditioned nledfumThe isolation of rat mieroglia from a primary culture of Day 1 rat brain and the preparation of mieroghal conditioned medium (Mic-CM) were described previously [5,12,13]. Mleroglial galls were allow~l to adhere to 6-or 12-well plates (Costar). After removal of nonattached ~ils, the miereglia were washed 3 times with serum-free Dulbeoeo'~ modified Eagle medium (DMEM), and incubated with 0 5 ml (for 12-well plates) or 1 ml (for 6-well plates) of the ~ame medium in the presence or absence of retinoie acid, IL-I (Genzymg)and bFGF (R&D Systems). The recovered conditioned medmm was centrifuged at 1,500 rpm rot 10 mm and tim supernatant was used for ELISA either ~mmediately or after storage at -80"C. Pur~icat/on of plazntttwgen attd preparation of the antibody...

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Section: Determination Of Plasminogen In Miccmsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Retinoic acid enhances the secretion of plasminogen from cultured rat microglia

Nakajima¹,

Takemoto²,

Kohsaka³

1992

FEBS Letters

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“…When stimulated, microglia acquire an ameboid morphology and present an upregulated catalog of surface molecules (Oehmichen & Gencic 1975, Cho et al 2006, such as MHC, chemokine receptors, and CD14 (Rock et al 2004). This activated state also coincides with the production of soluble mediators both detrimental, such as pro-inflammatory cytokines, reactive oxygen species, and reactive nitrogen species (Sawada et al 1989, Moss & Bates 2001, Viviani et al 2001, Liu et al 2002, Tansey et al 2007, and beneficial (i.e. anti-inflammatory cytokines and tropic factors) (Morgan et al 2004, Liao et al 2005, Muller et al 2006Fig.…”

Section: Neuroinflammation: the Main Featuresmentioning

confidence: 78%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

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“…The toxicity originates from in vitro studies that demonstrated neuronal survival is attenuated by exposure to both microglia treated with proinflammatory stimuli and the supernatant of the treated microglia [49,50]. These activated microglia release cytotoxic factors such as superoxide, nitric oxide, and tumor necrosis factor (TNF)-α [51][52][53][54][55]. Similarly, the detrimental role of activated microglia in vivo has been reported.…”

Section: Microgliamentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Production of tumor necrosis factor-alpha by microglia and astrocytes in culture

Cited by 591 publications

References 17 publications

Retinoic acid enhances the secretion of plasminogen from cultured rat microglia

Retinoic acid enhances the secretion of plasminogen from cultured rat microglia

Neuroactive steroids, their metabolites, and neuroinflammation

Microglia and Monocyte-Derived Macrophages in Stroke

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