The Role of GPNMB in Inflammation

Saade, Marina; Souza, Giovanna Araujo de; Scavone, Cristóforo; Kinoshita, Paula Fernanda

doi:10.3389/fimmu.2021.674739

Cited by 111 publications

(116 citation statements)

References 84 publications

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“…GPNMB is an endogenous glycoprotein, and many studies have found that it is related to inflammation and neuroinflammation. GPNMB is highly expressed in macrophages and microglia, which are involved in the innate immune response in the periphery and the brain, respectively [19]. GPNMB has been shown to increase the brain tissue of Parkinson's disease patients and reduce the inflammation of astrocytes [20].…”

Section: Discussionmentioning

confidence: 99%

Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB

Zhao

Cui

Zheng

et al. 2022

Applied Bionics and Biomechanics

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Objective. At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms. Methods. The in vitro and in vivo models of SAKI were established using lipopolysaccharide (LPS). Mel was injected intraperitoneally at 60 mg/kg into male C57BL/6 mice 4 hours before LPS injection (10 mg/kg). The HK-2 cells were treated with LPS (1 μg/mL) and Mel (40 μM). The renal function and renal pathological changes as well as renal inflammation and apoptosis were detected in SAKI mice. The inflammation and apoptosis of HK-2 cells induced by LPS were also detected. Results. The treatment of Mel significantly decreased the elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in SAKI mice. In addition, the results of HE staining suggested that Mel significantly reduced kidney damage in SAKI mice. Consistently, Mel reduced the expression of LPS-induced kidney injury markers (NGAL and KIM-1). Moreover, LPS induced the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the kidney, which can be reduced by Mel. Furthermore, Mel effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the kidneys of SAKI mice. Mechanistically, Mel inhibited the phosphorylation of P65 but induced the phosphorylation of AKT and the expression of glycoprotein B of nonmetastatic melanoma (GPNMB). However, knocking down GPNMB can eliminate the anti-inflammatory and antiapoptotic effects of Mel. Conclusion. Mel alleviated sepsis-induced kidney injury by inhibiting kidney inflammation and apoptosis via upregulating GPNMB.

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Section: Discussionmentioning

confidence: 99%

Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB

Zhao

Cui

Zheng

et al. 2022

Applied Bionics and Biomechanics

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“…It is expressed in many cell types, such as osteoblasts, melanocytes, hepatocytes and leukocytes. This protein, also named Osteoactivin, has a vast array of biological activities, being involved in processes of cell adhesion and differentiation, tissue remodeling and repair after injury; some studies also reported that GPNMB limits inflammation and inhibits T cell-mediated immune responses (Abdelmagid et al 2008 ; Safadi et al 2001 ; Shikano et al 2001 ; Haralanova-Ilieva et al 2005 ; Ripoll et al 2007 ; Kobayashi et al 2019 ; Chung et al 2020 ; Saade et al 2021 ; Weterman et al 1995 ; Singh et al 2010 ).…”

Section: Main Textmentioning

confidence: 99%

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

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Myeloid cells infiltrating tumors are gaining ever growing attention in the last years because their pro-tumor and immunosuppressive functions are relevant for disease progression and therapeutic responses. The functional ambiguity of tumor-associated macrophages (TAMs), mostly promoting tumor evolution, is a challenging hurdle. This is even more evident in the case of cancer stem cells (CSCs); as active participants in the specialized environment of the cancer stem cell niche, TAMs initiate a reciprocal conversation with CSCs. TAMs contribute to protect CSCs from the hostile environment (exogenous insults, toxic compounds, attacks from the immune cells), and produce several biologically active mediators that modulate crucial developmental pathways that sustain cancer cell stemness. In this review, we have focused our attention on the interaction between TAMs and CSCs; we describe how TAMs impact on CSC biology and, in turn, how CSCs exploit the tissue trophic activity of macrophages to survive and progress. Since CSCs are responsible for therapy resistance and tumor recurrence, they are important therapeutic targets. In view of the recent success in oncology obtained by stimulating the immune system, we discuss some macrophage-targeted therapeutic strategies that may also affect the CSCs and interrupt their malevolent alliance.

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“…We showed that higher plasma levels of the integral part of BBB, the tight junction component (TJP1 42 ), and proteins degrading it (AIMP1 43 and BIN1 44 ), increased the risk of dementias. Moreover, pro-inflammatory C1Q, C1R, CD20, CD11, CDHR5, GPNMB, and IL1β 45–49 elevated risk of dementias, whereas anti-inflammatory C4B, IL27, IL37, PTP1B, and SIGGIRR 50–54 and barrier protecting IL-17F 55 reduced the risk. In suppression and inhibition, regulatory T-cells suppress, or molecules on B- and T-cells inhibit activation of lymphocytes at peripheral checkpoints.…”

Section: Discussionmentioning

confidence: 99%

Immune system and blood-brain barrier-wide biomarker analyses provide causal evidence for autoimmunity in dementia

Lindbohm

Mars

Sipilä

et al. 2022

Preprint

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Immune system and blood brain barrier (BBB) dysfunction are implicated in the development of Alzheimers disease and other dementias, but their causal role remains unknown. We performed Mendelian randomization (MR) for 43,643 immune system and BBB-related biomarkers and identified 126 potential causal risk factors for dementias. A phenome-wide analysis using MR-based polygenic risk score in FinnGen study (N=339,233) for these risk factors revealed a common genetic background for dementias and autoimmune diseases which was supported by further HLA analyses. Pathway analyses linked the 126 proteins to amyloid-b, tau and a-synuclein pathways, increased inflammatory responses, and altered self-tolerance mechanisms. In inverse-probability-weighted analyses simulating randomized controlled drug trials in observational data, anti-inflammatory and immunosuppressive medications were associated with reduced dementia risk (p<0.01 for methotrexate and TNF-a inhibitors). These converging results from different research lines suggest that autoimmunity is a modifiable component in diseases causing dementia.

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The Role of GPNMB in Inflammation

Cited by 111 publications

References 84 publications

Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB

Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB

Macrophages and cancer stem cells: a malevolent alliance

Immune system and blood-brain barrier-wide biomarker analyses provide causal evidence for autoimmunity in dementia

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