Title:Th1/Th17 Cytokine Profile is Induced by Macrophage Migration Inhibitory Factor in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients
Volume: 18
Issue: 10
Author(s): Samuel García-Arellano*, Luis Alexis Hernández-Palma*, Richard Bucala, Jorge Hernández-Bello, Ulises De la Cruz-Mosso, Trinidad García-Iglesias, Sergio Cerpa-Cruz, Jorge Ramón Padilla-Gutiérrez, Yeminia Valle, José Guadalupe Soñanez-Organis, Isela Parra-Rojas, Ana Laura Pereira-Suárez and José Francisco Muñoz-Valle
Affiliation:
- Instituto de Investigacion en Ciencias Biomedicas, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco,Mexico
- Instituto de Investigacion en Ciencias Biomedicas, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco,Mexico
Keywords:
MIF, cytokines, Th1 profile, Th17 profile, PBMC, rheumatoid arthritis.
Abstract: Background: Macrophage migration inhibitory factor (MIF) is an
immunoregulatory cytokine that plays a crucial role as a regulator of the innate and
adaptive immune responses and takes part in the destructive process of the joint in
rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory
cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human
MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL-
17F in peripheral blood mononuclear cells (PBMC) from RA patients and control
subjects (CS).
Methods: The PBMC from RA patients and CS were stimulated for 24 hours with
combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were
measured using a multiplex immunoassay and, macrophage migration inhibitory factor
(MIF) was determined by ELISA kit.
Results: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation
with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated
PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in
comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ
(721.90 vs. 8.40 pg/mL, p<0.001), IL-1β (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70
vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43
vs. 0.92 pg/mL, p<0.001).
Conclusion: These results highlight the potential role of MIF in the establishment of the
chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and
provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in
PBMC from RA and CS.
