Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

Ramasatyaveni Geesala, Neha R. Dhoke, Amitava Das

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. Methods BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure. Inflammatory cell infiltration and temporal expression of inflammatory cytokines at the wound bed were determined using immunohistochemical and quantitative-real time polymerase chain reaction (qPCR) analysis, respectively. Mechanistic studies were performed on a murine macrophage cell line (J774.2) to evaluate the effect of interleukin (IL)-17A. Results Celecoxib administration led to a significantly high percent of wound closure, cellular proliferation, collagen deposition, BMSCs engraftment and re-epithelialization at the wound site. Interestingly, recruitment of CD4+T cells and F4/80+ macrophages as well as BMSC transplantation induced up-regulation of Cox-2 and IL-17A gene expression levels were reverted by celecoxib administration. Exogenous supplementation of recombinant interleukin (rIL)-17 to J774.2 cells significantly increased proliferation and gene expression of cytokines -IL-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α via nuclear translocation of nuclear factor kappa B (NFκB)p65/50 subunit. Conditioned media of rIL-17 treated J774.2 cells when supplemented to BMSCs depicted a dose-dependent increase in the number of apoptotic cells and proapoptotic protein expression that was perturbed by celecoxib or IL-17 neutralizing antibody. Finally, celecoxib led to a dose-dependent increase in BMSC differentiation into keratinocyte-like cells in vitro. Conclusion Celecoxib protects transplanted BMSCs from Cox-2/IL-17–induced inflammation and increases their engraftment, differentiation into keratinocytes and re-epithelialization thereby potentiating wound tissue repair.

Original languageEnglish (US)
Pages (from-to)756-770
Number of pages15
Issue number6
StatePublished - Jun 1 2017
Externally publishedYes


  • Cyclooxygenase-2
  • bone marrow stem cells
  • engraftment
  • inflammation
  • interleukin-17
  • nuclear factor kappa B
  • re-epithelialization
  • transplantation
  • wound repair

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation


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