The role of expression and activity of 15-Lipoxygenase isoforms and related cytokines in patients with Multiple Sclerosis and healthy controls

Abstract

Background: Multiple Sclerosis (MS) as an inflammatory multifactorial auto immune nervous system disease imposes devastating burden of morbidity worldwide. Among environmental and genetic factors, the relevance of inflammatory mediators in MS pathogenesis is well documented. 15-Lipoxygense enzyme and its derived products have received attention as possible mediators of inflammatory responses. The involvement of 15-Lipoxygense pathway in the pathogenesis of inflammatory diseases such as MS has yet to be illustrated which is perused in the current study.

Methods: The expression level of 15-Lipoxygense isoforms was assessed via Real-Time PCR in the peripheral blood mononuclear cells separated from patients with MS and healthy subjects. The level of 15-Lipoxygense products (15(S) HETE, 13(S) HODE) and related cytokines (IL4 and IL13) were evaluated using enzyme immunoassay kits in serum samples.

Results: Our results demonstrated that 15-Lipoxygense-1 and 15-Lipoxygense-2 expression levels were increased in patients suffering from MS comparing to healthy subjects which were more obvious in Relapsing-Remitting MS. The elevated levels of 15-Lipoxygense isoforms were accompanied with 15(S) HETE and 13(S) HODE enhancement in serum of patients and the IL 13 elevation but not IL4 was consistent with higher expression of 15-Lipoxygense. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups.

Conclusion: The possible effect of 15-Lipoxygense pathway in the regulation of inflammatory events may light up new therapeutic possibilities regarding MS pathogenesis.

Keywords: 13(S) HODE; 15(S) HETE; 15-Lipoxygense; IL 13; IL4; Multiple sclerosis.