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Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase‐2 during periodontitis
Author(s) -
Hirschfeld Josefine,
Howait Mohammed,
Movila Alexandru,
Parčina Marijo,
BekeredjianDing Isabelle,
Deschner James,
Jepsen Søren,
Kawai Toshihisa
Publication year - 2017
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12363
Subject(s) - macrophage migration inhibitory factor , proinflammatory cytokine , inflammation , porphyromonas gingivalis , cytokine , periodontitis , glucocorticoid , tumor necrosis factor alpha , medicine , matrix metalloproteinase , endocrinology , periodontal pathogen , chemistry , immunology , biology
Macrophage migration inhibitory factor ( MIF ) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids ( GC s). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF – GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 ( MMP ‐2) during periodontitis, in vivo and in vitro. In a Mif ‐knockout ( KO ) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 ( IL ‐6), MIF , MMP ‐2, and corticosterone. In addition, human gingival fibroblasts ( HGF s) were tested for production of IL ‐6 and MMP ‐2 after stimulation with hydrocortisone ( HC ), MIF , tumour necrosis factor‐alpha ( TNF ‐ α ), or Fusobacterium nucleatum , a pathogen known to elicit immune responses during periodontitis. Wild‐type ( WT ) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL ‐6 concentrations. Systemic GC levels were reduced in WT and Mif ‐ KO mice during inflammation, with overall lower concentrations in Mif ‐ KO mice. In vivo and in vitro, MMP ‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC . Therefore, MIF does not appear to stimulate expression of MMP ‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP ‐2. Our findings further suggest that MIF may regulate systemic GC levels.