Background Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important role in the development and pathogenesis of rheumatoid arthritis (RA). MIF promotes the expression of cytokines related to RA development, as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-17. Two polymorphisms in the promoter of the MIF gene have been associated with increased production of protein and it has been shown that TNF-α is involved in the regulation of MIF mRNA expression and protein secretion in a dose-dependent manner.
Objectives To evaluate the effect of MIF gene haplotypes on rhTNF-α and rhMIF response in peripheral blood mononuclear cells (PBMC) of RA patients
Methods Genotyping was performed for MIF gene haplotypes in 230 RA patients. Cell culture of PBMC from two patients per homozygous haplotype (5G, 6G and 7C) was performed and stimulated with rhTNF-α and rhMIF. Cytokine levels were analyzed by a microsphere-based ELISA method (Bio-Plex® MAGPIX™).
Results rhTNF-α and rhMIF-induced IL-6, IL-17A and IL-17F secretion in PBMC of RA patients. We observed that PBMC extracted from patients with MIF 7C haplotypes stimulated with rhTNF showed higher secretion of IL-17A and IL-17F than patients with 5G and 6G haplotypes. IL-6 production with rhMIF stimulation was more pronounced in the 5G haplotype group than 6G or 7C haplotype groups.
Conclusions rhTNF-α and rhMIF promote differential secretion of IL-6, IL-17A and IL-17F according to MIF haplotypes presence. IL-17A and IL-17F secretion of stimulated PBMC with rhTNF-α are higher in patients with 7C haplotype than non-7C haplotypes. Furthermore, IL-6 levels are higher in PBMC from patients with 5G haplotype stimulated with MIF than non-5G haplotypes.
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Acknowledgements This study was supported by funding from the National Council of Science and Technology (CONACYT) Grant #161749 assigned to JFMV.
Disclosure of Interest None declared