Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders

Abstract

Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and tumoricidal activity. It has been reported that MIF is associated with the pathogenesis of a variety of diseases. MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis. In experimental inflammatory disease, blockade of MIF bioactivity inhibited the severity of disease activity. On the other hand, MIF expression is also increased in tumor lesions, and MIF plays a role as a cell growth factor. MIF has been reported to be constitutively expressed in gut, liver, and pancreas. In patients with gastritis, inflammatory bowel disease, hepatitis, and pancreatitis, MIF expression was remarkably increased in both the serum and the local lesions. Blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis, colitis, hepatitis, and pancreatitis. On the other hand, MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro. Blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro. MIF plays important roles in the pathogenesis of gastrointestinal, hepatic, and pancreatic disorders.

Monocyte Subsets and Natural Killer Cells in Acute Pancreatitis

“…Excessive inflammatory reaction known as systemic inflammatory response syndrome complicated by multisystem organ failure is considered as a leading cause of death in early AP [3][4][5] . So far, the evaluation of the role of mononuclear cells in this phenomenon has been focused on the monocyte/macrophage system, indicating strong activation of this system [7,[30][31][32] .…”

Diagnostic Validity of Serum Macrophage Inhibitor Cytokine and Tissue Polypeptide-Specific Antigen in Pancreatobiliary Diseases

“…It participates in inflammation, immune response, and cell proliferation and differentiation. It has effects on the growth of tumor cells as well as non-tumor cells in the process of wound repair [20]. Experimental studies have reported that MIC-1 is expressed in various gastrointestinal tissues including the stomach, intestine, liver and pancreas.…”

Antagonism of macrophage migration inhibitory factor decreases cyclophosphamide cystitis in mice

“…[3][4][5][6] In addition, MIF is rather unique in that it possesses enzymatic tautomerase activity. [7][8][9] Although the physiological role for MIF's tautomerase activity remains to be discovered, blocking MIF's tautomerase activity can also block MIF's biological activity.…”