The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling

Song, Hualin; Shen, Qi; Zhou, Tianjun; Jin, Jie

doi:10.1242/bio.053447

Cited by 10 publications

(13 citation statements)

References 29 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We next used pharmacological probes to verify these surprising results. The MIF small molecule inhibitor ISO-1 (4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid methyl ester) binds to the tautomerase pocket of MIF, thereby inhibiting its catalytic activity as well as its CD74-mediated induction of MAPK activation, p53-dependent apoptosis and cell proliferation ( 43–45 ). ISO-1 was previously also shown to partially block the MIF-CXCR4 reporter activation ( 39 ) and MDL1-induced monocyte chemotaxis ( 33 ), indicating that this inhibitor might likewise affect MDL1/CXCR4 effects.…”

Section: Resultsmentioning

confidence: 99%

Section: Synergy By Mif and Mdls On Human Chemokine Receptor Activationmentioning

confidence: 99%

See 1 more Smart Citation

Structures ofArabidopsis thalianaMDL Proteins and Synergistic Effects with the Cytokine MIF on Human Receptors

Spiller

Manjula

Leissing

et al. 2023

Preprint

View full text Add to dashboard Cite

Vertebrates have developed effective immune mechanisms to fight microbial attacks, relying on a sophisticated network of innate and adaptive responses, a circulatory system, and numerous orchestrating soluble mediators such as cytokines. Mammalian macrophage migration inhibitory factor (MIF) and its paralog D-dopachrome tautomerase (D-DT/MIF-2) are multifunctional inflammatory cytokines with chemokine-like properties that modulate immunity. Plants possess orthologous MIF/D-DT-like (MDL) proteins, whose function is largely unexplored. Driven by the previous discovery of cross-kingdom mimicry of plant (Arabidopsis thaliana) MDL proteins and human MIF receptor signaling, we here characterized the structures of the threeA. thalianaMDLs by X-ray crystallography and explored the mechanism underlying the interplay between plant MDLs, human MIF, and its receptors. We obtained high-resolution structures at 1.56 Å, 1.40 Å, and 2.00 Å resolution for MDL1, MDL2, and MDL3, respectively, revealing a typical trimeric assembly and a high three-dimensional similarity to human MIF. Although residues at the catalytic site of the three MDLs show high identity to human MIF, the proteins showed low tautomerase activity for the substrate 4-hydroxyphenylpyruvate (HPP). Structural differences likely explain the enzymatic inactivity of plant MDLs for HPP. Strikingly, employingin vitro,in vivo, andin plantatest systems, we found that MIF and MDL proteins interact with each other and have the capacity to form hetero-oligomeric complexes. The functional consequences of this interaction were demonstrated applying a yeast-based reporter system specific for the MIF chemokine receptors CXCR2 and CXCR4. MDLs not only triggered receptor signaling on their own, but exhibited pronounced synergism regarding the activation of the CXCR2- and CXCR4-dependent signaling pathways, when co-applied with MIF. These findings were substantiated by the co-administration of pharmacological inhibitors that either disrupt MIF receptor binding or block the catalytic cavity. Moreover, biochemical and biophysical experiments using an allosteric oligomer-specific MIF inhibitor established hexa-oligomer formation between MIF and MDLs as the putative basis for the synergistic effect. Our results are the starting point for a mechanistic understanding of the immunomodulatory activity of a family of highly conserved plant proteins.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Synergy By Mif and Mdls On Human Chemokine Receptor Activationmentioning

confidence: 99%

Structures ofArabidopsis thalianaMDL Proteins and Synergistic Effects with the Cytokine MIF on Human Receptors

Spiller

Manjula

Leissing

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Together, MIF is highly expressed in BPH epithelium. In vitro , MIF promoted BPH epithelial cell growth by regulating COX-2 and P53 signaling ( 30 ) ( Figure 1 ).…”

Section: The Role Of Inflammation In Bphmentioning

confidence: 99%

Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

et al. 2022

View full text Add to dashboard Cite

To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: “benign prostatic hyperplasia”, “inflammation”, “pathogenesis” and “disease development”. Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.

show abstract

“…Inflammation have been reported to promote the progression of benign prostatic hyperplasia (BPH) (64). Meta-Analysis suggested BPH is associated with an increased risk of prostate cancer, especially in Asian BPH patients (65).…”

Section: O-glcnacylation Implicates In Precancerous Inflammation Lesi...mentioning

confidence: 99%

O-GlcNAcylation and Its Role in Cancer-Associated Inflammation

Ouyang

Deng

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post-translational modification (PTM) of serine and threonine residues of proteins, O-linked-N-Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.

show abstract

The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling

Cited by 10 publications

References 29 publications

Structures ofArabidopsis thalianaMDL Proteins and Synergistic Effects with the Cytokine MIF on Human Receptors

Structures ofArabidopsis thalianaMDL Proteins and Synergistic Effects with the Cytokine MIF on Human Receptors

Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

O-GlcNAcylation and Its Role in Cancer-Associated Inflammation

Contact Info

Product

Resources

About