Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats

Abstract

BackgroundInflammatory responses in brain are primarily mediated by microglia, but growing evidence suggests a crucial importance of astrocytes. S100B, a calcium-binding protein secreted by astrocytes, has properties of a neurotrophic or an inflammatory cytokine. However, it is not known whether primary signals occurring during induction of an inflammatory response (e.g. lipopolysaccharide, LPS) directly modulate S100B.MethodsIn this work, we evaluated whether S100B levels in cerebrospinal fluid (CSF) and serum of Wistar rats are affected by LPS administered by intraperitoneal (IP) or intracerebroventricular (ICV) injection, as well as whether primary astrocyte cultures respond directly to lipopolysaccharide.ResultsOur data suggest that S100B secretion in brain tissue is stimulated rapidly and persistently (for at least 24 h) by ICV LPS administration. This increase in CSF S100B was transient when LPS was IP administered. In contrast to these S100B results, we observed an increase in in TNFα levels in serum, but not in CSF, after IP administration of LPS. In isolated astrocytes and in acute hippocampal slices, we observed a direct stimulation of S100B secretion by LPS at a concentration of 10 μg/mL. An involvement of TLR4 was confirmed by use of specific inhibitors. However, lower levels of LPS in astrocyte cultures were able to induce a decrease in S100B secretion after 24 h, without significant change in intracellular content of S100B. In addition, after 24 h exposure to LPS, we observed a decrease in astrocytic glutathione and an increase in astrocytic glial fibrillary acidic protein.ConclusionsTogether, these data contribute to the understanding of the effects of LPS on astrocytes, particularly on S100B secretion, and help us to interpret cerebrospinal fluid and serum changes for this protein in neuroinflammatory diseases. Moreover, non-brain S100B-expressing tissues may be differentially regulated, since LPS administration did not lead to increased serum levels of S100B.

Kallikrein 6 is a novel molecular trigger of reactive astrogliosis

“…To begin to understand the functional significance of stellation to the process of astrogliosis, we compared the effects of KLK6 to those of LPS, a pro-inflammatory component of the cell wall of gram-negative bacteria, which is known to promote astrocyte activation IN VITRO (Brahmachari et al, 2006) and IN VIVO (Guerra et al, 2011). Notably, like KLK6, LPS promoted robust stellation of primary astrocytes.…”

Resveratrol Protects Hippocampal Astrocytes Against LPS-Induced Neurotoxicity Through HO-1, p38 and ERK Pathways

“…Lipopolysaccharide (LPS) is the main component of outer membrane of gran-negative bacteria and has been widely used to study experimentally inflammatory response, including in the CNS [11,12]. In this sense, astrocytes have TLR4, which belongs to TLR family receptors, and specifically recognizes LPS [12,13].…”

“…In this sense, astrocytes have TLR4, which belongs to TLR family receptors, and specifically recognizes LPS [12,13]. The exposure to LPS can lead to release of proinflammatory cytokines and it in turn activate the transcription factor NFjB, nitric oxide (NO) release and overproduction of reactive oxygen species (ROS) [11,14].…”

Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in hippocampal astrocytes through the heme oxygenase-1 pathway

“…Lipopolysaccharide (LPS), the main component of the outer membrane of Gram-negative bacteria, has been used as a classical model of innate recognition, which leads to a robust inflammatory response by activation of immunocompetent cells [10,11]. On the cellular level, LPS induces changes in protein expression, which is triggered by its binding to Tolllike receptor 4 (TLR4), which is present in astrocytes [10,12].…”

“…On the cellular level, LPS induces changes in protein expression, which is triggered by its binding to Tolllike receptor 4 (TLR4), which is present in astrocytes [10,12]. Exposure to LPS can lead to the translocation of nuclear factor kappa B (NFκB) into the nucleus, inducing the transcription of inflammatory genes, nitric oxide (NO) release, and the overproduction of ROS [10][11][12]. Therefore, it is likely that activation of NFκB that occurs in astrocytes following neuroinflammation plays a key role in the pathophysiology of the development of CNS disorders.…”