Haptoglobin Function and Regulation in Autoimmune Diseases

Abstract

Haptoglobin (Hp) is an acute phase protein, primarily synthesized in the liver and secreted into the plasma. Hp is also produced in other tissues including lung, skin, spleen, brain, intestine, arterial vessels and kidney, but to a lesser extent (D'Armiento et al., 1997; Pelletier et al., 1998; Yang et al., 2000). The normal concentration in human plasma ranges from 0.33 mg/ml and increases several fold in the occurrence of local or systemic inflammation. Increased production of Hp is the result of transcriptional activation of the Hp gene (Baumann & Jahreis, 1983; Oliviero et al., 1987) by pro-inflammatory cytokines such as interleukin(IL)-1, IL-6, and Tumor Necrosis factor (TNF) (Baumann et al., 1989). The result of pro-inflammatory cytokine signalling is the activation of essential transcription factors that are needed for the expression of Hp (STAT, C/EBP, PEA3). Among vertebrate species, the promoter of the Hp gene is conserved and contains three key regulatory elements that include two C/EBP recognition sequences that flank a STAT binding site (Wang et al., 2001).