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Molecular Medicine

, Volume 17, Issue 11–12, pp 1132–1132 | Cite as

Response to Comment on “Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis”

  • Karla C. Queiroz
  • C. Arnold Spek
Letters to the Editor
  • 16 Downloads

In our recent work, we used genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction-dependent KC production in colon epithelial cells, which provokes granulocyte influx leading to subsequent inflammation and organ damage. We agree with Gambone et al. (1) that experiments using genetically modified mice should ideally be performed with littermate controls. Unfortunately, intercrosses of 50% TF mice are problematic, and using this strategy resulted in insufficient TFlow (1%) mice within a similar age category as littermate wild-type controls. Consequently, we opted for an experimental setup in which littermate 1% and 50% TF mice were compared with nonlittermate C57BL/6 wild types. The 1% and 50% TF mice had been backcrossed for six generations with C57BL/6 mice and are thus largely on a C57BL/6 genetic background (2). However, we performed a control experiment to exclude potential strain differences biasing our results. To this end, wild-type mice obtained from an intercross of 50% TF mice were compared with nonlittermate wild-type C57BL/6 mice in the DSS-induced experimental colitis model as described in our report (3). In this particular experiment, we did not observe differences between the groups with respect to body weight loss, increase in colon weight, reduction in colon length and disease severity score. Unfortunately, however, disease symptoms were rather mild and somewhat variable (perhaps resulting from a new batch of DSS). After careful consideration, we decided not to include these data in the published report. Despite the limitations of this control experiment, we are confident the differences presented in our report are indeed due to changes in TF levels and not due to strain differences.

Disclosure

The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.

References

  1. 1.
    Gambone JE, Owens AP III, Mackman N. (2011) Comment on “Tissue factor-dependent chemokine production aggravates experimental colitis.” Mol. Med. 17:1131.CrossRefGoogle Scholar
  2. 2.
    Parry GC, Erlich JH, Carmeliet P, Luther T, Mackman N. (1998) Low levels of tissue factor are compatible with development and hemostasis in mice. J. Clin. Invest. 101:560–9.CrossRefGoogle Scholar
  3. 3.
    Queiroz KC, et al. (2011) Tissue factor-dependent chemokine production aggravates experimental colitis. Mol. Med. 17:1119–26.PubMedPubMedCentralGoogle Scholar

Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  1. 1.Center for Experimental and Molecular MedicineAcademic Medical CenterAmsterdamThe Netherlands

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