Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes

Godina-González, Susana; Furuzawa‐Carballeda, Janette; Utrera-Barillas, Dolores; Alcocer‐Varela, Jorge; Teran, Luis M.; Mercado, Mónica Vázquez-Del; Leal, Yelda A.; Alvarado‐Cabrero, Isabel; Velázquez, Juan R.

doi:10.1007/s00011-010-0224-2

Cited by 11 publications

(3 citation statements)

References 22 publications

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“…Previous investigations have reported that MAPK pathway is involved in the biological actions of MLIF[ 46 ]. As a group of MAPK families, JNK pathway plays an important role in apoptosis by destabilize p53 and promote ubiquitin-mediated degradation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2

et al. 2016

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Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide, has been shown to exert potent anti-inflammatory effects in ischemic brain injury. In this study, we investigated the neuroprotective action of MLIF against oxygen-glucose deprivation (OGD)-induced injury in human neuroblastoma SH-SY5Y cells. MTT assay was used to assess cell viability, and flow cytometry assay and Hoechst staining were used to evaluate apoptosis. LDH assay was used to exam necrosis. The release of inflammatory cytokines was detected by ELISA. Levels of the apoptosis associated proteins were measured by western blot analysis. To identify the protein target of MLIF, pull-down assay and mass spectrometry were performed. We observed that MLIF enhanced cell survival and inhibited apoptosis and necrosis by inhibiting p-JNK, p53, c-caspase9 and c-caspase3 expression. In the microglia, OGD-induced secretion of inflammatory cytokines was markedly reduced in the presence of MLIF. Furthermore, we found that eukaryotic translation elongation factor 1A2 (eEF1A2) is a downstream target of MLIF. Knockdown eEF1A2 using short interfering RNA (siRNA) almost completely abrogated the anti-apoptotic effect of MLIF in SH-SY5Y cells subjected to OGD, with an associated decrease in cell survival and an increase in expression of p-JNK and p53. These results indicate that MLIF ameliorates OGD-induced SH-SY5Y neuroblastoma injury by inhibiting the p-JNK/p53 apoptotic signaling pathway via eEF1A2. Our findings suggest that eEF1A2 may be a new therapeutic target for ischemic brain injury.

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Section: Discussionmentioning

confidence: 99%

MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2

et al. 2016

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“…It is also reported that MLIF can inhibit the expression of interleukin-1␤, interferon-␥, interleukin-5, and interleukin-6 and increase the expression of interleukin-10 in macrophages. [11][12][13][14][15][16] The anti-inflammatory effect of MLIF led us to the initial interest to test whether it can act inflammatory response in brain ischemia. We 17 and other laboratories 18 have found MLIF can remarkably protect brain ischemic injury with decreased ischemic volume changes.…”

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confidence: 99%

A Pentapeptide Monocyte Locomotion Inhibitory Factor Protects Brain Ischemia Injury by Targeting the eEF1A1/Endothelial Nitric Oxide Synthase Pathway

Zhang

Fan

Liu

et al. 2012

Stroke

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Background and Purpose-Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia. Methods-A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry. Results-MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression. Conclusions-In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway. (Stroke. 2012;43:2764-2773.)

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“…Expression profiling by high throughput sequencing data sets was obtained from Gene Expression Omnibus (GEO). GSE14721: Articular tissue from collagen–induced arthritis (CIA) (vs. adjuvant ctrl) 27 ; GSE13071: Knee joint synovium from CIA (vs. naïve ctrl) 28 ; GSE167190: Whole ankle tissue from collagen antibody–induced arthritis (CAIA) (vs. LPS ctrl) 29 ; GSE71599: K/BxN serum–transfer arthritis (STA) synovium (vs. PBS ctrl) 30 ; GSE89408: RA synovial biopsies (vs. Osteoarthritis) 31 ; GSE77298: RA synovial biopsies (vs. healthy ctrl) 32 ( Figure 1A ). Enrichment analysis was performed using Metascape 33 ( https://metascape.org/ ) ( Figure 1B ).…”

Section: Methodsmentioning

confidence: 99%

Bub1 suppresses inflammatory arthritis–associated bone loss in mice through inhibition of TNFα–mediated osteoclastogenesis

Yoshida,

Ikedo,

Yanagihara

et al. 2024

Journal of Bone and Mineral Research

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Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovitis, bone and cartilage destruction, and increased fracture risk with bone loss. Although disease-modifying anti-rheumatic drugs (DMARDs) have dramatically improved clinical outcomes, these therapies are not universally effective in all patients due to the heterogeneity of RA pathogenesis. Therefore, it is necessary to elucidate the molecular mechanisms underlying RA pathogenesis, including associated bone loss, in order to identify novel therapeutic targets. In this study, we found that Budding uninhibited by benzimidazoles 1 (BUB1) was highly expressed in RA patients’ synovium and murine ankle tissue with arthritis. As CD45+CD11b+ myeloid cells are a Bub1 highly expressing population among synovial cells in mice, myeloid cell-specific Bub1 conditional knockout (Bub1ΔLysM) mice were generated. Bub1ΔLysM mice exhibited reduced femoral bone mineral density (BMD) when compared to control mice under K/BxN serum-transfer arthritis (STA), with no significant differences in joint inflammation or bone erosion based on a semi-quantitative erosion score and histological analysis. Bone histomorphometry revealed that femoral bone mass of Bub1ΔLysM under arthritis was reduced by increased osteoclastic bone resorption. RNA-seq and subsequent Gene Set Enrichment Analysis (GSEA) demonstrated a significantly enriched NF-κB pathway among up-regulated genes in RANKL-stimulated bone marrow-derived macrophages (BMMs) obtained from Bub1ΔLysM mice. Indeed, osteoclastogenesis using BMMs derived from Bub1ΔLysM was enhanced by RANKL and TNFα or RANKL and IL-1β treatment compared to controls. Finally, osteoclastogenesis was increased by Bub1 inhibitor BAY1816032 treatment in BMMs derived from wildtype mice. These data suggest that Bub1 expressed in macrophages plays a protective role against inflammatory arthritis-associated bone loss through inhibition of inflammation-mediated osteoclastogenesis.

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Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes

Abstract: MLIF could be an interesting new molecule to investigate in the field of rheumatoid arthritis pathogenesis research for its potential to prevent inflammation.

Cited by 11 publications

References 22 publications

MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2

MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2

A Pentapeptide Monocyte Locomotion Inhibitory Factor Protects Brain Ischemia Injury by Targeting the eEF1A1/Endothelial Nitric Oxide Synthase Pathway

Bub1 suppresses inflammatory arthritis–associated bone loss in mice through inhibition of TNFα–mediated osteoclastogenesis

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