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Updated: Jul 4, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis
Jaya Talreja1, Changya Peng1, Lobelia Samavati1,2
1Department 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.
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.
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