title: Macrophage migration inhibitory factor: a regulator of MMP13 and inflammation in titanium particles-stimulated air pouch in vivo.
abstract: Macrophage migration inhibitory factor (MIF) is a significant regulator of inflammatory diseases, and local inflammation plays an important role in the aseptic loosening of failed total hip arthroplasty (THA). A high-level MIF expression was found in the interfacial membrane around implants. However, the cause of increased MIF expression and the action of MIF in the process of aseptic-loosening implant is still unknown. This study is to investigate MIF expression and its upregulating effect on matrix metalloproteinases (MMPs) expression in the particles-stimulated air pouches in mice that appear to closely resemble the interfacial membranes. A total of 48 murine air pouches were divided into four groups, and were injected with PBS, titanium particles suspensions, titanium particles suspensions with neutralizing antibody of MIF, and titanium particles suspensions with normal IgG, respectively. Histological and cytokine responses were evaluated. The inflammatory reaction of air pouch membranes induced by titanium particles was significantly suppressed by neutralizing antibody. The levels of MIF protein and mRNA were significantly increased in the titanium particles-stimulated air pouch membranes compared with the control groups. So were the levels of MMP13 protein and mRNA. However, the levels of MMP13 protein and mRNA were significantly reduced by neutralizing antibody. Our study demonstrates that titanium particles can cause the air pouch membranes to increase the expression of MIF, which upregulates the production of MMP13 and induces inflammatory reaction in vivo. The results indicate that MIF may play an important role in the process of aseptic-loosening implants after THA.
authors.affiliation: Orthopaedic Department, The Sixth Affiliated People's Hospital, Medical School of ShangHai JiaoTong University, 200233 ShangHai, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pan
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014025:Titanium / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D014025:Titanium; D053509:Matrix Metalloproteinase 13; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse