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Activation of CD147 with Cyclophilin A Induces the Expression of IFITM1 through ERK and PI3K in THP-1 Cells

DOI: 10.1155/2010/821940

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CD147, as a receptor for Cyclophilins, is a multifunctional transmembrane glycoprotein. In order to identify genes that are induced by activation of CD147, THP-1 cells were stimulated with Cyclophilin A and differentially expressed genes were detected using PCR-based analysis. Interferon-induced transmembrane 1 (IFITM1) was detected to be induced and it was confirmed by RT-PCR and Western blot analysis. CD147-induced expression of IFITM1 was blocked by inhibitors of ERK, PI3K, or NF- B, but not by inhibitors of p38, JNK, or PKC. IFITM1 appears to mediate inflammatory activation of THP-1 cells since cross-linking of IFITM1 with specific monoclonal antibody against it induced the expression of proinflammatory mediators such as IL-8 and MMP-9. These data indicate that IFITM1 is one of the pro-inflammatory mediators that are induced by signaling initiated by the activation of CD147 in macrophages and activation of ERK, PI3K, and NF- B is required for the expression of IFITM1. 1. Introduction Interferon-induced transmembrane (IFITM/Mil/fragilis) proteins, originally described based on their expression after IFN treatment [1], belong to a superfamily that is characterized by the presence of two transmembrane domains and an intervening highly conserved intracellular loop. Over 30 members of this superfamily are known to be involved in antiviral defense, immune cell signaling, cell adhesion, oncogenesis, and germ cell maturation [2–6]. As the first identified member of this superfamily, IFITM1 (CD225) has been studied for its involvement in the inhibition of viral replication [7], promotion of cancer cell invasion [8], and expression in transformed cells as a cancer marker [9–12]. CD147 (EMMPRIN/basigin/HAb18G/neurothelin/M6/TCSF) has two immunoglobulin-like extracellular domains and a short (39 amino acids long) intracellular domain [13]. CD147 plays a critical role in many pathological and physiological processes in a variety of cell types such as cancer cells, leukocytes, fibroblasts, and endothelial cells [14–17]. Stimulation of CD147 in fibroblast and endothelial cells has been shown to facilitate tumor invasion, metastasis, and angiogenesis [17, 18]. On the other hand, stimulation of CD147 in leukocytes leads to the enhancement of a variety of inflammatory processes that are associated with atherosclerosis, lung injury, rheumatoid arthritis (RA), chronic liver disease, and heart failure [19–21]. Two members of cyclophilin family, cyclophilin A and B (CypA and CypB), can interact and stimulate CD147 [22, 23]. These cyclosporine binding proteins can be


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