Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis

Abstract

Experimental autoimmune neuritis (EAN) is an animal model of Guillain–Barré syndrome, an inflammatory demyelination disease of the peripheral nervous system. Although this disease has been extensively studied on peripheral nerves, the pathology of the central nervous system has not been fully understood. Previous studies demonstrate that expression of keratan sulfate (KS), the sugar chain of proteoglycan, is associated with activated microglia/macrophages accumulated after neuronal injuries. Unexpectedly, we found here that KS is rather diminished in rat EAN. KS was restrictively expressed in microglia in the spinal cord of normal rats. KS was positive in 50% microglia in the ventral horn and 20% in the dorsal horn. In EAN, microglia increased in number and expressed the activation marker CD68, but KS expression was abolished. Concomitantly, pro-inflammatory cytokines, i.e., interferon (IFN)-γ, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, were increased in the spinal cord of EAN rats, whereas anti-inflammatory cytokines, such as IL-4 and IL-10, were decreased. In addition, silencing of KSGal6ST attenuated KS expression on the primary cultured microglia and upregulated expression of some activation markers (TNF-α, IL-1β, and iNOS) under the stimulation with lipopolysaccharide and IFN-γ. This study demonstrates for the first time a close association of EAN and disappearance of KS on microglia. KS expression could be a useful marker to evaluate the status of polyneuropathy.

Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain-Barré syndrome

“…Matsui et al (25) reported that IL-1β, TNF-α and IFN-γ were increased in the spinal cord of EAN rats, whereas anti-inflammatory cytokines, including IL-4 and IL-10, were decreased (25). Serum IFN-γ was also elevated in patients with GBS (26).…”

Dietary Keratan Sulfate from Shark Cartilage Modulates Gut Microbiota and Increases the Abundance of Lactobacillus spp.

“…Additionally, KS also actively participates in the development of neural system [5,6]. Much more recently, KS was evidenced to be involved in the microbial infection process of corneal stroma and the progress of experimental autoimmune neuritis [1,7]. Taken together, KS plays a biologically important role in various physiological processes, and, as a promising drug candidate, it has been developed as an active ingredient in different pharmaceutical formulations [1].…”

Keratan sulfate: An up-to-date review

“…In the work of Matsui and co-authors, the investigators have shown for the first time a negative correlation between the expression of KS by microglia and the progress of the experimental auto-immune neuritis (EAN) [14]. In this pathology, a demyelination process characterizes the auto-immunological response on cells of the peripheral nervous system.…”

“…In this pathology, a demyelination process characterizes the auto-immunological response on cells of the peripheral nervous system. Matsui and coworkers had the goal of studying the role of KS in this immunological process [14]. They noticed that KS expression is fairly diminished in cases of EAN rat models.…”

“…[19][20][21] KS is seen fairly diminished in microglia of spine cord (main tissue of the central nervous system responsible for KS synthesis) during auto-immune neuritis. [14] Cancer biology KS can be used as a biomarker in carcinomas of female genital tract.…”