Abstract
BackgroundNoradrenaline (NA) is known to limit neuroinflammation. However, the previously described induction by NA of a chemokine involved in the progression of immune/inflammatory processes, such as chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein-1 (MCP-1), apparently contradicts NA anti-inflammatory actions. In the current study we analyzed NA regulation of astroglial chemokine (C-X3-C motif) ligand 1 (CX3CL1), also known as fractalkine, another chemokine to which both neuroprotective and neurodegenerative actions have been attributed. In addition, NA effects on other chemokines and pro-inflammatory mediators were also analyzed.MethodsPrimary astrocyte-enriched cultures were obtained from neonatal Wistar rats. These cells were incubated for different time durations with combinations of NA and lipopolysaccharide (LPS). The expression and synthesis of different proteins was measured by RT-PCR and enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassays. Data were analyzed by one-way analysis of variance (ANOVA), followed by Newman-Keuls multiple comparison tests.ResultsThe data presented here show that in control conditions, NA induces the production of CX3CL1 in rat cultured astrocytes, but in the presence of an inflammatory stimulus, such as LPS, NA has the opposite effect inhibiting CX3CL1 production. This inversion of NA effect was also observed for MCP-1. Based on the observation of this dual action, NA regulation of different chemokines and pro-inflammatory cytokines was also analyzed, observing that in most cases NA exerts an inhibitory effect in the presence of LPS. One characteristic exception was the induction of cyclooxygenase-2 (COX-2), where a summative effect was detected for both LPS and NA.ConclusionThese data suggest that NA effects on astrocytes can adapt to the presence of an inflammatory agent reducing the production of certain cytokines, while in basal conditions NA may have the opposite effect and help to maintain moderate levels of these cytokines.
Highlights
Noradrenaline (NA) is known to limit neuroinflammation
The present study describes the induction of Chemokine ligand 1 (CX3CL1) expression and synthesis by NA in astrocytes
NA induces CX3CL1 synthesis and release in astrocytes An enzyme-linked immunosorbent assay (ELISA) assay was used to evaluate the production of CX3CL1 and its release from cultured astrocytes
Summary
Noradrenaline (NA) is known to limit neuroinflammation. the previously described induction by NA of a chemokine involved in the progression of immune/inflammatory processes, such as chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein-1 (MCP-1), apparently contradicts NA anti-inflammatory actions. In the current study we analyzed NA regulation of astroglial chemokine (C-X3-C motif) ligand 1 (CX3CL1), known as fractalkine, another chemokine to which both neuroprotective and neurodegenerative actions have been attributed. In relation to the study of mechanisms involved in the development of diseases with a neurological component, the main attribute of NA is its ability to reduce the neuroinflammatory processes associated to them [5]. Diverse experimental settings indicate that NA interactions with different types of brain cells lead to the regulation of inflammatory pathways and mediators [5]. We have focused our work on the analysis of NA interaction with astrocytes, to help elucidate the means through which NA protects neurons against different types of injuries
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