Short Report

Hepcidin is elevated in mice injected with Mycoplasma arthritidis

Curry L Koening¹ , Hong-Hua Mu¹ , Adam Van Schelt¹ , Eric Lo² , Diane M Ward² , Jerry Kaplan² and Ivana De Domenico³

¹  Division of Rheumatology, Department of Internal Medicine, University of Utah, School of Medicine, 30 North 1900 East, Salt Lake City, 84132, Utah, USA

²  Department of Pathology, University of Utah, School of Medicine, 30 North 1900 East, Salt Lake City, 84132, Utah, USA

³  Division of Hematology, Department of Internal Medicine, University of Utah, School of Medicine, 30 North 1900 East, Salt Lake City, 84132, Utah, USA

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Journal of Inflammation 2009, 6:33doi:10.1186/1476-9255-6-33

Published:	24 November 2009

Abstract

Mycoplasma arthritidis causes arthritis in specific mouse strains. M. arthritidis mitogen (MAM), a superantigen produced by M. arthritidis, activates T cells by forming a complex between the major histocompatability complex II on antigen presenting cells and the T cell receptor on CD4+ T lymphocytes. The MAM superantigen is also known to interact with Toll-like receptors (TLR) 2 and 4. Hepcidin, an iron regulator protein, is upregulated by TLR4, IL-6, and IL-1. In this study, we evaluated serum hepcidin, transferrin saturation, ferritin, IL-6, IL-1, and hemoglobin levels in M. arthritidis injected C3H/HeJ (TLR2^+/+, TLR4^-/-) mice and C3H/HeSnJ (TLR2^+/+, TLR4^+/+) mice over a 21 day period. C3H/HeJ mice have a defective TLR4 and an inability to produce IL-6. We also measured arthritis severity in these mice and the amount of hepcidin transcripts produced by the liver and spleen. C3H/HeJ mice developed a more severe arthritis than that of C3H/HeSnJ mice. Both mice had an increase in serum hepcidin within three days after infection. Hepcidin levels were greater in C3H/HeJ mice despite a nonfunctioning TLR4 and low serum levels of IL-6. Splenic hepcidin production in C3H/HeJ mice was delayed compared to C3H/HeSnJ mice. Unlike C3H/HeSnJ mice, C3H/HeJ mice did not develop a significant rise in serum IL-6 levels but did develop a significant increase in IL-1β during the first ten days after injection. Both mice had an increase in serum ferritin but a decrease in serum transferrin saturation. In conclusion, serum hepcidin regulation in C3H/HeJ mice does not appear to be solely dependent upon TLR4 or IL-6.