Increased CXCL10 expression in MS MSCs and monocytes is unaffected by AHSCT

Bonechi, Elena; Aldinucci, Alessandra; Mazzanti, Benedetta; Gioia, Massimo Di; Repice, Anna Maria; Manuelli, Cinzia; Saccardi, Riccardo; Massacesi, Luca; Ballerini, Clara

doi:10.1002/acn3.92

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…4 b). A previous study indicated that one of the transcription factors of the PI3K-AKT pathway, CREB, may be involved in the transcription of CXCL10 [ 23 ]. To verify this, we treated CD115(+) precursors with BYL719, GSK690693, 666–15 and rapamycin, which are a PI3K antagonist, AKT antagonist, CREB antagonist and mTOR antagonist, respectively, to test their effects on the expression of CXCL10.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies have revealed that the PI3K pathway participates in the regulation of CXCL10 [ 21 , 46 ] and that inhibiting the PI3K pathway downregulates the production of CXCL10 and affects CXCL10 gene promoter activity, which is consistent with the findings of this study. Furthermore, a previous study showed that CREB is involved in the expression of CXCL10 [ 23 ]. Here, we revealed that inhibiting the transcription factor CREB directly can downregulate the expression of CXCL10.…”

Section: Discussionmentioning

confidence: 99%

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Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer

Qian

Gong

Zhang³

et al. 2021

Cell Commun Signal

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Background To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors. Methods The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts. Results LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate. Conclusion LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer

Qian

Gong

Zhang³

et al. 2021

Cell Commun Signal

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“…Reasons for this include: failure of CXCL10- specific mAbs to inhibit all CXCR3 ligands, inability of anti-CXCL10 mAbs to compete with the high synthesis and turnover rate of CXCL10, and inability of some anti-CXCL10 mAbs to bind the glycosaminoglycan (GAG) bound form of CXCL10 (the active form of CXCL10). Importantly, SLAMF7-mediated inhibition of alpha chemokines has the ability to overcome all of these limitations and may find itself to be a useful therapeutic modality in diseases where over-expression of CXCL10 has been linked to pathogenesis including: rheumatoid arthritis (51), type I diabetes mellitus (52), systemic lupus erythematous (53), multiple sclerosis (54), ulcerative colitis (55), and primary biliary cirrhosis (56).…”

Section: Discussionmentioning

confidence: 99%

SLAMF7 Is a Critical Negative Regulator of IFN-α–Mediated CXCL10 Production in Chronic HIV Infection

O’Connell

Pepelyayeva

Blake

et al. 2019

The Journal of Immunology

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Current advances in combined anti-retroviral therapy (cART) have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The immune cell receptor SLAMF7 has been shown to be upregulated in diseases characterized by chronic immune activation. Here, we studied the function of the SLAMF7 receptor in immune cells of HIV patients and the impacts of SLAMF7 signaling on peripheral immune activation. We observed increased frequencies of SLAMF7+ PBMCs in HIV+ individuals in a clinical phenotype-dependent manner, with discordant and long-term nonprogressor patients showing elevated SLAMF7 levels, and elite controllers showing levels comparable to healthy controls. We also noted that SLAMF7 was sensitive to IFN⍺ stimulation; a factor elevated during HIV infection. Further studies revealed SLAMF7 to be a potent inhibitor of the monocyte-derived proinflammatory chemokine CXCL10 (IP-10) and other CXCR3 ligands, except in a subset of HIV+ patients termed SLAMF7 silent (SF7S). Studies utilizing small molecule inhibitors revealed that the mechanism of CXCL10 inhibition is independent of known SLAMF7 binding partners. Furthermore, we determined that SLAMF7 activation on monocytes is able to decrease their susceptibility to HIV-1 infection in vitro via down-regulation of CCR5 and up-regulation of the CCL3L1 chemokine. Finally, we discovered that neutrophils do not express SLAMF7, are CXCL10+ at baseline, are able to secrete CXCL10 in response to IFN⍺ and LPS, and are non-responsive to SLAMF7 signaling. These findings implicate the SLAMF7 receptor as an important regulator of IFN⍺-driven innate immune responses during HIV infection.

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“…TLR4 expression was significantly increased in bone marrow mesenchymal stem cells (MSCs) and peripheral monocytes of MS, activating its downstream molecules STAT-1, NF-κB, P38, JNK and CREB, increasing the production of CXCL10 and promoting inflammatory responses ( 51 ). Pertussis toxin (PTX), an adjuvant in inducing EAE, depended on TLR4 signaling molecules to facilitate T cell infiltration into the CNS ( 52 , 53 ).…”

Section: Role Of Tlrs In Neuroimmune Diseasesmentioning

confidence: 99%

Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems

Liu

Han

et al. 2021

Front. Immunol.

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Toll-like receptors (TLRs) are a class of proteins playing a key role in innate and adaptive immune responses. TLRs are involved in the development and progression of neuroimmune diseases via initiating inflammatory responses. Thus, targeting TLRs signaling pathway may be considered as a potential therapy for neuroimmune diseases. However, the role of TLRs is elusive and complex in neuroimmune diseases. In addition to the inadequate immune response of TLRs inhibitors in the experiments, the recent studies also demonstrated that partial activation of TLRs is conducive to the production of anti-inflammatory factors and nervous system repair. Exploring the mechanism of TLRs in neuroimmune diseases and combining with developing the emerging drug may conquer neuroimmune diseases in the future. Herein, we provide an overview of the role of TLRs in several neuroimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorder, Guillain-Barré syndrome and myasthenia gravis. Emerging difficulties and potential solutions in clinical application of TLRs inhibitors will also be discussed.

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Increased CXCL10 expression in MS MSCs and monocytes is unaffected by AHSCT

Cited by 9 publications

References 27 publications

Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer

Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer

SLAMF7 Is a Critical Negative Regulator of IFN-α–Mediated CXCL10 Production in Chronic HIV Infection

Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems

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