Introduction
Guillain–Barré syndrome (GBS) is a common autoimmune disease
characterized pathologically by inflammation and demyelination in the
peripheral nervous system (PNS) [1,
2]. Experimental autoimmune neuritis
(EAN) is a classic animal model of GBS, which has been widely used in
basic research of GBS [3,
4]. After activation, macrophages can be
divided into pro-inflammatory M1 macrophages and anti-inflammatory M2
macrophages, and recently, new research found that M3 switch phenotype
also existed [5,
6]. In GBS and EAN, M1 macrophages are
involved in the inflammatory impairment of the myelin sheath through
promoting cellular cytotoxicity and producing Th1 cytokines. M2
macrophages contribute to repairing myelin and axon by promoting Th2
immune response and the secretion of anti-inflammatory cytokines
[7-9]. Several studies have
demonstrated that the switch from M1 to M2 could effectively ameliorate
the severity of EAN [7,
10, 11].
Nuclear factor-κB (NF-κB) is a inducible transcription factor expressed
in a large number of cells and involved in immune and inflammatory
responses [12]. Moreover, the
activated form p65 of NF-κB has been observed in the sural nerve
macrophages of acute and chronic inflammatory demyelinating
polyneuropathy (AIDP, CIDP), and the sciatic nerves of rats with EAN,
suggesting NF-κB attribute to the inflammatory demyelination. So far
there are very few studies demonstrating the role of NF-κB in the course
of macrophage polarized [13,
14]. However, the research results on
the relationship between macrophages and NF-κB in this process have been
controversial.
The objective of this study was to assess the effect of M2 macrophages
in treating EAN and to explore the role of NF-κB regulating macrophage
subtype. Our results showed that M2 macrophages is effective in treating
EAN by inhibiting the activation of NF-κB p65 and the production of
pro-inflammatory cytokines. The inhibitor of NF-κB, BAY11-7082
attenuates the severity of EAN by inhibiting NF-κB pathway and the
polarization of M1 macrophages.