Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease

Angela Sena, Irina Grishina, Anne Thai, Larissa Goulart, Monica Macal, Anne Fenton, Jay Li, Thomas P Prindiville, Sonia Maria Oliani, Satya Dandekar, Luiz Goulart, Sumathi Sankaran-Walters

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background:Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression.Methods:ANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.Results:We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.Conclusion:Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.

Original languageEnglish (US)
Article numbere76969
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 10 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease'. Together they form a unique fingerprint.

  • Cite this

    Sena, A., Grishina, I., Thai, A., Goulart, L., Macal, M., Fenton, A., Li, J., Prindiville, T. P., Oliani, S. M., Dandekar, S., Goulart, L., & Sankaran-Walters, S. (2013). Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease. PLoS One, 8(10), [e76969]. https://doi.org/10.1371/journal.pone.0076969