Astrocyte and Macrophage Regulation of YKL‐40 Expression and Cellular Response in Neuroinflammation

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.

Short-Term and Long-Term Effects of Dexamethasone on Cognitive Dysfunction Induced by Sevoflurane in Adult Rats

“…Neuroinflammation is a cornerstone of degenerative changes and cognitive disease (3,17). However, the cognitive impairment induced by anaesthetics may depend on different factors, and it was recently shown that sevoflurane leads to increased interleukin-6 (IL-6) levels and induces neuroinflammation and cognitive disorders in young mice (18).…”

YKL‐40: The Search for New Biomarkers in Rheumatoid Arthritis

“…Proinlammatory interleukins, such as IL-2, IL-6, IL-12, IL-13, IL-17, and IL-18, did not induce YKL-40 transcription in astrocytes [23], while IL-6 and IL-17 showed enhanced production in human primary chondrocyte culture [22,24].…”

Serum YKL-40 levels as a prognostic factor in patients with intracerebral hemorrhage

“…A positive correlation between the severity of the disease state and the levels of YKL-40 in either cerebrospinal fluid or sera of patients with a variety of pathological conditions has been demonstrated in the recent clinical studies, and most have speculated that YKL-40 might be a valuable biochemical marker of inflammation, similar to C-reactive protein [5][6][7][8][9][10][11][12][13][14][15]. YKL-40 can also be expressed in astrocytes and may take part in acute neuroinflammation [16][17][18]. In the general population, elevated plasma YKL-40 levels are associated with increased risk of ischemic stroke and ischemic cerebrovascular disease, independently of plasma C-reactive protein levels [19].…”