Serum Cyclophilin A Correlates with Increased Tissue MMP-9 in Patients with Ulcerative Colitis, but Not with Crohn's Disease

Dig Dis Sci. 2017 Jun;62(6):1511-1517. doi: 10.1007/s10620-017-4568-0. Epub 2017 Apr 8.

Abstract

Background: Cyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied.

Aim: This study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients.

Methods: Serum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study. We measured serum and tissue level of CyPA, and tissue level of TNF-α, MMP-9, TIMP-1/MMP-9, and TIMP-2/MMP-9 using ELISA method.

Results: Our results indicated that serum, but not tissue CyPA is increased in UC, rather than in CD patients, compared to the control. The increase correlated with higher tissue concentration of MMP-9 and TNF-α, especially in the UC group. Moreover, we observed significantly higher level of TIMP-1/MMP-9 in UC and CD group, which overlapped with the change in MMP-9. There was no change in TIMP-2/MMP-9 in the analyzed groups.

Conclusion: The current study suggests that serum CyPA may be an independent additional marker of IBD, especially of UC. Higher CyPA level may be followed by increased MMP-9 in those patients. However, further studies are necessary to verify the role of CyPA in IBD development.

Keywords: Crohn’s disease; Cyclophilin A; Matrix metalloproteinase 9; Tissue inhibitor of metalloproteinase; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biopsy
  • Case-Control Studies
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology*
  • Cyclophilin A / blood*
  • Cyclophilin A / metabolism
  • Female
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 9
  • Cyclophilin A