British Journal of Nutrition

Full Papers

Human and Clinical Nutrition

Expression of iron-related proteins in the duodenum is up-regulated in patients with chronic inflammatory disorders

Abitha Sukumarana1, Jithu Jamesa1, Harish Palleti Janardhana1, Anita Amaladasa1, Lekshmy Madathilazhikathu Suresha1, Debashish Dandaa2, Visalakshi Jeyeseelana3, Balakrishnan Siddharth Ramakrishnaa4 and Molly Jacoba1 c1

a1 Department of Biochemistry, Christian Medical College, Vellore, Tamil Nadu 632002, India

a2 Department of Rheumatology and Clinical Immunology, Christian Medical College, Vellore, Tamil Nadu 632004, India

a3 Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu 632002, India

a4 Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu 632004, India

Abstract

Mechanisms responsible for derangements in Fe homeostasis in chronic inflammatory conditions are not entirely clear. The aim of the present study was to test the hypothesis that inflammation affects the expression of Fe-related proteins in the duodenum and monocytes of patients with chronic inflammatory disorders, thus contributing to dysregulated Fe homeostasis. Duodenal mucosal samples and peripheral blood monocytes obtained from patients with chronic inflammatory disorders, namely ulcerative colitis (UC), Crohn's disease (CD) and rheumatoid arthritis, were used for gene and protein expression studies. Hb levels were significantly lower and serum C-reactive protein levels were significantly higher in patients in the disease groups. The gene expression of several Fe-related proteins in the duodenum was significantly up-regulated in patients with UC and CD. In patients with UC, the protein expression of divalent metal transporter 1 and ferroportin, which are involved in the absorption of dietary non-haem Fe, was also found to be significantly higher in the duodenal mucosa. The gene expression of the duodenal proteins of interest correlated positively with one another and negatively with Hb. In patients with UC, the gene expression of Fe-related proteins in monocytes was found to be unaffected. In a separate group of patients with UC, serum hepcidin levels were found to be significantly lower than those in the control group. In conclusion, the expression of Fe-related proteins was up-regulated in the duodenum of patients with chronic inflammatory conditions in the present study. The effects appeared to be secondary to anaemia and the consequent erythropoietic drive.

(Received March 14 2013)

(Revised September 10 2013)

(Accepted September 11 2013)

(Online publication October 25 2013)

Key Words:

  • Anaemia;
  • Hepcidin;
  • Inflammatory bowel disease;
  • Iron;
  • Monocytes

Correspondence

c1 Corresponding author: M. Jacob, fax +91 416 2262788, email mjacob@cmcvellore.ac.in

Footnotes

  Abbreviations: ACD, anaemia of chronic disease; CD, Crohn's disease; CRP, serum C-reactive protein; dcytb, duodenal cytochrome b; DMT1, divalent metal transporter 1; GDF15, growth differentiation factor 15; IBD, inflammatory bowel disease; IDA, Fe-deficiency anaemia; MACS, magnetic-activated cell sorter; RA, rheumatoid arthritis; TfR1, transferrin receptor 1; TWSG1, twisted gastrulation factor 1; UC, ulcerative colitis

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