MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis

Jaya Talreja; Changya Peng; Lobelia Samavati

doi:10.1016/j.isci.2023.108746

MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis

iScience. 2023 Dec 14;27(1):108746. doi: 10.1016/j.isci.2023.108746. eCollection 2024 Jan 19.

Authors

Jaya Talreja¹, Changya Peng¹, Lobelia Samavati^{1

2}

Affiliations

¹ Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University, School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
² Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.

Abstract

Macrophage migration inhibitory factor (MIF) is a versatile cytokine that influences a variety of cellular processes important for immune regulation and tissue homeostasis. Sarcoidosis is a granulomatous disease characterized by extensive local inflammation and increased T helper cell mediated cytokines. We have shown that MIF has a modulatory role in cytokine networks in sarcoidosis. We investigated the effect of exogenous MIF on sarcoidosis alveolar macrophages (AMs), CD14⁺ monocytes and peripheral blood mononuclear cells (PBMCs). Our results showed that MIF negatively regulates the increased MAPKs (pp38 and pERK1/2) activation by inducing Mitogen-activated protein kinase phosphatase (MKP)-1. We found that MIF decreased IL-6 and IL-1β production, increased the percentage of regulatory T-cells (Tregs), and induced IL-1R antagonist (IL-1RA) and IL-10 production. Thus, the results of our study suggest that exogenous MIF modulates MAPK activation by inducing MKP-1and Tregs as well as IL-10 and IL-1RA, and hence plays a modulatory role in immune activation in sarcoidosis.

Keywords: Immunology; Molecular biology.

Grants and funding

R01 HL113508/HL/NHLBI NIH HHS/United States