Effect of apolipoprotein E on secretions of matrix metalloproteinase-9, matrix metalloproteinase tissue inhibitor-1 and inflammatory factors in macrophages at early stage of experimental autoimmune encephalomyelitis

Objective To explore the effect of apolipoprotein E (ApoE) on secretions of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase tissue inhibitor-1 (TIMP-1) and inflammatory factors in spleen macrophages at early stage of experimental autoimmune encephalomyelitis (EAE). Methods In accordance with random number table, 20 ApoE knockout (ApoE-/-) C57BL/6J mice were divided into ApoE-/- EAE group and ApoE-/- control group (n=10); and 20 wild type (WT) C57BL/6J mice were divided into WT EAE group and WT control group (n=10). Myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) was used as antigen to induce EAE models in the ApoE-/- EAE group and WT EAE group, and MOG35-55 was replaced by normal saline in ApoE-/- control group and WT control group. The spleen macrophages were isolated from mice after 7th d of modeling and cultured in vitro; the macrophages of the ApoE-/- EAE group and WT EAE group were stimulated by MOG35-55, while the macrophages of the ApoE-/- control group and WT control group were treated with equivalent normal saline. Forty-eight h after that, the contents of MMP-9, TIMP-1, interferon gamma-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the culture medium were determined by ELISA. Results The contents of MMP-9, IFN-γ, TNF-α and IL-6 in the WT EAE group were significantly higher than those in the WT control group (P<0.05); the contents of MMP-9, IFN-γ、TNF-α and IL-6 in the ApoE-/- EAE group were significantly higher than those in the ApoE-/- control group (P<0.05); the content of MMP-9, IFN-γ, TNF-α and IL-6 in ApoE-/- EAE group were significantly higher than those in the WT EAE group (P<0.05). The TIMP-1 secretion of macrophages in WT EAE group was significantly higher than that in WT control group (P<0.05). Conclusions At early stage of EAE, macrophages secrete high levels of MMP-9 and inflammatory factors, and the deficiency of ApoE further contributes to the secretions of MMP-9 and inflammatory factors by macrophages. ApoE may play a role in protecting the integrity of blood-brain barrier and alleviating the inflammatory response of the central nervous system through the effects on macrophages. Key words: Apolipoprotein E; Experimental autoimmune encephalomyelitis; Macrophage; Matrix metalloproteinase-9; Matrix metalloproteinase tissue inhibitor-1; Inflammatory factor