Anti-inflammatory nuclear receptor superfamily in multiple sclerosis patients from Sardinia and Sweden

作者：Liu XA; Steffensen KR; Sanna A; Arru G; Fois ML; Rosati G; Sotgiu S; Link H; Gustafsson JA; Huang YM^*

来源：Neurobiology of Disease, 2005, 20(3): 961-968.

DOI：10.1016/j.nbd.2005.06.001

• multiple sclerosis
• liver X reccptors
• estrogen receptors
• androgen receptor
• Sardinia

Several nuclear hormone receptors have been associated with inflammatory reactions. Particularly, liver X receptors (LXRs) have recently been identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, the MS incidence is lower, except on the island of Sardinia where the incidence is even higher than in Sweden. Subjects from Sardinia are ethnically more homogeneous, and differ from Swedes also regarding genetic background and environment We studied mRNA expression of several nuclear hormone receptors in blood mononuclear cells (MNC) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia, and Stockholm, Sweden. Sex- and age-matched healthy controls (HC) were from both areas. mRNA expression was evaluated by quantitative real-time PCR. We found altered mRNA expression of LXRs, estrogen receptors (ERs), and androgen receptor (AR) in MS. mRNA expression of both LXR alpha and LXR beta is lower in MS from Stockholm but not from Sassari. In particular, LXR alpha mRNA expression was significantly lower in MS from Stockholm as compared with all groups in the study including MS from Sassari. Low levels of ER(x mRNA are seen in MS from both Stockholm and Sassari. The splice variant EP beta cx showed significantly higher mRNA expression in MS from Sassari and Stockholm as compared with corresponding HC. In particular, ER beta cx mRNA in MS from Sassari was remarkably higher as compared with all other groups in the study. Higher levels of AR mRNA are present in HC from Sassari. The findings indicate that the expression levels of anti-inflammatory nuclear receptor superfamily genes in MS appear to reflect both ethnic and environmental influences.

• 出版日期2005-12