%0 Journal Article
%T A Possible Molecular Mechanism of Immunomodulatory Activity of Bilirubin
%A Hideto Isogai
%A Noriaki Hirayama
%J International Journal of Medicinal Chemistry
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/467383
%X Bilirubin is an endogenous product of heme degradation in mammals. Bilirubin has long been considered as a cytotoxic waste product that needs to be excreted. However, increasing evidence suggests that bilirubin possesses multiple biological activities. In particular, recent studies have shown that bilirubin should be a protective factor for several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Since these autoimmune diseases are closely associated with specific types of human leukocyte antigens (HLAs), we have hypothesized that bilirubin might bind to the antigenic peptide-binding groove of the HLA molecules and exert its immunosuppressive actions. In order to evaluate the hypothesis, theoretical docking studies between bilirubin and the relevant HLA molecules have been undertaken. The in silico studies have clearly shown that bilirubin may bind to the antigenic peptide-binding groove of the HLA molecules relevant to the autoimmune diseases with significant affinity. The bound bilirubin may block the binding of antigenic peptides to be presented to T cell receptors and lead to suppression of the autoimmune responses. Based on this hypothesis new drug discovery research for autoimmune diseases will be conducted. 1. Introduction Bilirubin is an end product of heme degradation in mammals. Although bilirubin has long been considered as a cytotoxic waste product, the beneficial properties of bilirubin have been identified during the last few decades. One possible physiologic role of bilirubin is as an antioxidant [1], and most current studies on the physiological functions of bilirubin focus on this effect. Although other functions of bilirubin besides the antioxidant effects are not well documented, increasing evidence suggests that bilirubin possesses potential immunomodulatory properties. In particular, recent studies have suggested that bilirubin effectively suppresses several autoimmune diseases. Liu and colleagues have demonstrated that bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis (EAE) [2]. Fischman and colleagues have shown that higher serum total bilirubin levels are protective against rheumatoid arthritis (RA) based on the secondary analysis of National Health and Nutrition Examination Survey data collected between 2003 and 2006 [3]. Peng and colleagues have observed that serum bilirubin concentrations in patients with multiple sclerosis (MS) are significantly reduced [4]. V¨Ētek and colleagues have found that serum bilirubin
%U http://www.hindawi.com/journals/ijmc/2013/467383/