Possible involvement of satellite glial cell–derived lipocalin-2 in dermatitis not itch-related behavior of atopic dermatitis model mice

Abstract

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with intractable itch. Dorsal root ganglion (DRG) plays an important role in signal transduction of itch. It has been reported that satellite glial cells (SGC) present around DRG neurons are involved in pain and itch through interactions with DRG neurons. However, it is unclear what factors in SGC are involved in inducing dermatitis and itch in DRG. In this study, we found that the expression of lipocalin-2 (LCN2) was increased in SGC of AD model NC/Nga mouse. Therefore, we also examined whether SGC-derived lipocalin-2 is involved in the induction of dermatitis and itch-related behavior in this model mice. Materials and methods: AD-like dermatitis was induced by the application of Dermatophagoides farinae body ointment to NC/Nga mice (AD-NC/Nga mice). Protein and gene expression in the DRG and spinal cord of AD-NC/Nga mice were examined. The effect of the LCN2 antibody on dermatitis pathology in AD-NC/Nga mice was confirmed. Results: LCN2 expression in DRG of AD-NC/Nga mice was higher than that of control NC/Nga mice. Immunohistochemical analysis revealed that LCN2 was expressed on SGC in DRG. Gene expression level of LCN2 in the DRG was significantly increased faster than in the spinal cord during the process of induction of AD-like dermatitis. LCN2 increased gene expression of MMP-9 in mouse DRG. Intrathecally administrated anti-LCN2 antibody twice a week for 3 weeks at the same time as induction of AD-like dermatitis reduced dermatitis score without inhibiting scratching behavior. Discussion: In conclusion, our data suggest that SGC-derived LCN2 is involved in the pathogenesis of dermatitis rather than itch-related behavior in AD-NC/Nga mice.