Cell and Tissue Research

, Volume 364, Issue 2, pp 415–427 | Cite as

Possible involvement of inflammatory/reparative processes in the development of uterine fibroids

  • Olga Protic
  • Paolo Toti
  • Md Soriful Islam
  • Rossella Occhini
  • Stefano Raffaele Giannubilo
  • William H. Catherino
  • Saverio Cinti
  • Felice Petraglia
  • Andrea Ciavattini
  • Mario Castellucci
  • Boris Hinz
  • Pasquapina Ciarmela
Regular Article

Abstract

Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the “usual leiomyoma”, characterized by overexpression of ECM proteins, whereas the “cellular type” has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the “usual type”. Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the “usual type”, we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the “cellular type”, stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.

Keywords

Usual leiomyoma Cellular leiomyoma Inflammation ECM Myofibroblast CD34 TNF-α Activin A Myometrium 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Olga Protic
    • 1
  • Paolo Toti
    • 2
  • Md Soriful Islam
    • 1
    • 3
  • Rossella Occhini
    • 2
  • Stefano Raffaele Giannubilo
    • 4
  • William H. Catherino
    • 5
  • Saverio Cinti
    • 1
    • 6
  • Felice Petraglia
    • 7
  • Andrea Ciavattini
    • 4
  • Mario Castellucci
    • 1
  • Boris Hinz
    • 8
  • Pasquapina Ciarmela
    • 1
    • 9
  1. 1.Department of Experimental and Clinical Medicine, Faculty of MedicinePolytechnic University of MarcheAnconaItaly
  2. 2.Department of Medical BiotechnologyUniversity of SienaSienaItaly
  3. 3.Biotechnology and Microbiology Laboratory, Department of BotanyUniversity of RajshahiRajshahiBangladesh
  4. 4.Department of Clinical SciencePolytechnic University of MarcheAnconaItaly
  5. 5.Department of Obstetrics and GynecologyUniformed Services University of the Health SciencesBethesdaUSA
  6. 6.Center of ObesityPolytechnic University of Marche – United HospitalsAnconaItaly
  7. 7.Department of Molecular and Developmental Medicine, Obstetrics, and GynecologyUniversity of SienaSienaItaly
  8. 8.Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of DentistryUniversity of TorontoTorontoCanada
  9. 9.Department of Information EngineeringPolytechnic University of MarcheAnconaItaly

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