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Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation
Dafna Bonneh-Barkay1, Stephanie J Bissel, Julia Kofler
1Department of Pathology, University of Pittsburgh, PA, USA. dafnabb@yahoo.com
Abstract:
Numerous inflammatory conditions are associated with elevated YKL-40 expression by infiltrating macrophages. Thus, we were surprised to observe minimal macrophage and abundant astrocyte expression of YKL-40 in neuroinflammatory conditions. The aims of the current study were to better delineate this discrepancy, characterize the factors that regulate YKL-40 expression in macrophages and astrocytes and study whether YKL-40 expression correlates with cell morphology and/or activation state. In vitro, macrophages expressed high levels of YKL-40 that was induced by classical activation and inhibited by alternative activation. Cytokines released from macrophages induced YKL-40 transcription in astrocytes that was accompanied by morphological changes and altered astrocytic motility. Because coculturing of astrocytes and macrophages did not reverse this in vitro expression pattern, additional components of the in vivo central nervous system (CNS) milieu must be required to suppress macrophage and induce astrocyte expression of YKL-40.
Insights
Neuroinflammation alters YKL-40 expression, with macrophages showing low levels and astrocytes showing high levels. This study investigated the regulation of YKL-40 in these cells during central nervous system (CNS) inflammation.
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- YKL-40 is typically elevated in macrophages during inflammation.
- A discrepancy exists, with low macrophage and high astrocyte YKL-40 observed in neuroinflammation.
Purpose of the Study:
- To investigate YKL-40 expression in macrophages and astrocytes in neuroinflammatory conditions.
- To characterize factors regulating YKL-40 in these cells.
- To correlate YKL-40 expression with cell morphology and activation.
Main Methods:
- In vitro cell culture of macrophages and astrocytes.
- Macrophage activation (classical and alternative).
- Cytokine analysis and YKL-40 transcription assessment.
Main Results:
- Macrophage YKL-40 was induced by classical activation and inhibited by alternative activation.
- Macrophage-derived cytokines induced YKL-40 transcription in astrocytes, altering their morphology and motility.
- In vitro coculturing did not replicate the in vivo expression pattern.
Conclusions:
- The central nervous system (CNS) milieu is crucial for suppressing macrophage and inducing astrocyte YKL-40 expression.
- Neuroinflammation uniquely regulates YKL-40 in astrocytes versus macrophages.
- Further research is needed to identify CNS-specific regulatory factors.
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