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Cited by 448

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Sustained Mitogen-activated Protein Kinase (MAPK) and Cytoplasmic Phospholipase A2 Activation by Macrophage Migration Inhibitory Factor (MIF)

Open access
Mitchell, Robert A., Metz, Christine N., Peng, Tina, Bucala, Richard·1999·Journal of Biological Chemistry

Abstract

Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory mediator with the unique ability to counter-regulate the inhibitory effects of glucocorticoids on immune cell activation. MIF is released from cells in response to glucocorticoids, certain pro-inflammatory stimuli, and mitogens and acts to regulate glucocorticoid action on the ensuing inflammatory response. To gain insight into the molecular mechanism of MIF action, we have examined the role of MIF in the proliferation and intracellular signaling events of the well characterized, NIH/3T3 fibroblast cell line. Both endogenously secreted and exogenously added MIFs stimulate the proliferation of NIH/3T3 cells, and this response is associated with the activation of the p44/p42 extracellular signal-regulated (ERK) mitogen-activated protein kinases (MAP). The MIF-induced activation of these kinases was sustained for a period of at least 24 h and was dependent upon protein kinase A activity. We further show that MIF regulates cytosolic phospholipase A2 activity via a protein kinase A and ERK dependent pathway and that the glucocorticoid suppression of cytokine-induced cytoplasmic phospholipase A2 activity and arachidonic acid release can be reversed by the addition of recombinant MIF. These studies indicate that the sustained activation of p44/p42 MAP kinase and subsequent arachidonate release by cytoplasmic phospholipase A2 are important features of the immunoregulatory and intracellular signaling events initiated by MIF and provide the first insight into the mechanisms that underlie the pro-proliferative and inflammatory properties of this mediator.

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Metadata

Authors
Mitchell, R. A., Metz, C. N., Peng, T., & Bucala, R.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-06
Volume
274
Issue
25
Pages
18100-18106
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2049310294
Cited by
448
References
42
FWCI
5.34
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Sustained Mitogen-activated Protein Kinase (MAPK) and Cytoplasmic Phospholipase A2 Activation by Macrophage Migration Inhibitory Factor (MIF). https://app.cochat.ai/papers/10.1074/jbc.274.25.18100
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Mitchell, R. A., Metz, C. N., Peng, T., & Bucala, R. (1999). Sustained Mitogen-activated Protein Kinase (MAPK) and Cytoplasmic Phospholipase A2 Activation by Macrophage Migration Inhibitory Factor (MIF). Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.25.18100

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