Objective The macrophage migration inhibitory factor (MIF) in the plasma, hydrops articuli, and synovium, and its relationship with laboratory indexes in patients with rheumatoid arthritis (RA) were determined, for the purpose to reveal the role of MIF on the pathogenesis of RA. Methods MIF mRNA expression in PBMCs was detected by qPCR. Plasma MIF was measured by enzyme linked immunosorbent assay (ELISA). MIF in hydrops articuli and synovium from RA patients and OA patients was evaluated by immunofluorescence (IF) and immunohistochemistry (IHC). The relationship between MIF and laboratory indexes of RA patients was analyzed. Human fibroblast-like synoviocytes (FLS) were treated with recombinant human MIF, and expression of inflammatory factors was determined by qPCR. The matrix metalloproteinase (MMP) 9 and extracellular regulated protein kinases (ERK)1/2 in FLS with MIF treatment were detected. Results MIF is significantly increased in plasma and hydrops articuli in RA patients. The expression of multiple inflammatory factors and MMPs was increased in RA patients and in FLS with rhMIF treatment. MIF was correlated with laboratory indexes in RA patients. Mechanistically, MIF promoted production of MMP9 by FLS through the ERK1/2 pathway. Conclusion Our results indicated that increased MIF was correlated with disease activity of RA patients. These findings also suggested that MIF induced multiple inflammatory factors and MMP 9 in FLS via ERK 1/2 pathway.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • MIF plays a key role in the initiation of RA by promoting the expression of various inflammatory factors in FLS and MMPs. • This study provides a basis for MIF-targeted RA clinical therapy and for exploring the feasibility of MIF as a therapeutic target for RA. • Increased MIF correlates with disease activity in RA patients. </entry> </row> </tbody> </tgroup> </Table>

Increased macrophage migration inhibitory factor is associated with inflammation in patients with rheumatoid arthritis

期刊论文
发表日期：

2025年2月14日

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Haolin Wu,
Fanzhang Yin,
Yue Wang,
Zhicheng Tang,
Huiming Hong,
Tingting Jiang,
Junqiao Guo,
Xiaolei Ma,
Genhong Yao,
Huayong Zhang

摘要

Objective

The macrophage migration inhibitory factor (MIF) in the plasma, hydrops articuli, and synovium, and its relationship with laboratory indexes in patients with rheumatoid arthritis (RA) were determined, for the purpose to reveal the role of MIF on the pathogenesis of RA.

Methods

MIF mRNA expression in PBMCs was detected by qPCR. Plasma MIF was measured by enzyme linked immunosorbent assay (ELISA). MIF in hydrops articuli and synovium from RA patients and OA patients was evaluated by immunofluorescence (IF) and immunohistochemistry (IHC). The relationship between MIF and laboratory indexes of RA patients was analyzed. Human fibroblast-like synoviocytes (FLS) were treated with recombinant human MIF, and expression of inflammatory factors was determined by qPCR. The matrix metalloproteinase (MMP) 9 and extracellular regulated protein kinases (ERK)1/2 in FLS with MIF treatment were detected.

Results

MIF is significantly increased in plasma and hydrops articuli in RA patients. The expression of multiple inflammatory factors and MMPs was increased in RA patients and in FLS with rhMIF treatment. MIF was correlated with laboratory indexes in RA patients. Mechanistically, MIF promoted production of MMP9 by FLS through the ERK1/2 pathway.

Conclusion

Our results indicated that increased MIF was correlated with disease activity of RA patients. These findings also suggested that MIF induced multiple inflammatory factors and MMP 9 in FLS via ERK 1/2 pathway.

Key Points

• MIF plays a key role in the initiation of RA by promoting the expression of various inflammatory factors in FLS and MMPs.

• This study provides a basis for MIF-targeted RA clinical therapy and for exploring the feasibility of MIF as a therapeutic target for RA.

• Increased MIF correlates with disease activity in RA patients.