Inhibiting effects of Leflunomide metabolite on overexpression of CD147, MMP-2 and MMP-9 in PMA differentiated THP-1 cells

Huang, Junshen; Wu, Shiyao; Xie, Xiang; Wang, Mingxia; Zhu, Shangling; J, Gu

doi:10.1016/j.ejphar.2011.07.045

Cited by 19 publications

(14 citation statements)

References 37 publications

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“…Both Teri or MMF act on microglia and monocytes via the inhibition of nuclear factor kappa-light-chain-enhancer (NF-κB) [31, 32]. It was postulated that Teri reduces mRNA production of pro-inflammatory factors matrix metalloproteinase (MMP) 2 and MMP9 in monocytes [33]. In addition to the inhibition of mitochondrial DHODH, Teri decreased the release of IL-6 and CCL2 from activated monocytes in vitro, presumably in a DHODH independent manner [11].…”

Section: Discussionmentioning

confidence: 99%

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Ambrosius

Faissner

Guse

et al. 2017

J Neuroinflammation

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HIV-associated neurocognitive disorders (HAND) affect about 50% of infected patients despite combined antiretroviral therapy (cART). Ongoing compartmentalized inflammation mediated by microglia which are activated by HIV-infected monocytes has been postulated to contribute to neurotoxicity independent from viral replication. Here, we investigated effects of teriflunomide and monomethylfumarate on monocyte/microglial activation and neurotoxicity. Human monocytoid cells (U937) transduced with a minimal HIV-Vector were co-cultured with human microglial cells (HMC3). Secretion of pro-inflammatory/neurotoxic cytokines (CXCL10, CCL5, and CCL2: p < 0.001; IL-6: p < 0.01) by co-cultures was strongly increased compared to microglia in contact with HIV-particles alone. Upon treatment with teriflunomide, cytokine secretion was decreased (CXCL10, 3-fold; CCL2, 2.5-fold; IL-6, 2.2-fold; p < 0.001) and monomethylfumarate treatment led to 2.9-fold lower CXCL10 secretion (p < 0.001). Reduced toxicity of co-culture conditioned media on human fetal neurons by teriflunomide (29%, p < 0.01) and monomethylfumarate (27%, p < 0.05) indicated functional relevance. Modulation of innate immune functions by teriflunomide and monomethylfumarate may target neurotoxic inflammation in the context of HAND.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0829-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Ambrosius

Faissner

Guse

et al. 2017

J Neuroinflammation

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“…LY294002, SP600125, and PD98059 were all purchased from Sigma (USA). A-172 cells were transfected with a VEGFa-overexpressing plasmid [17], or a small short hairpin-interfering RNA for VEGFa (shVEGFa) [18], or MMP2-overexpressing plasmid, or a small short hairpin-interfering RNA for MMP2 (shMMP2) [19], as has been previously described [20]. The plasmid construct also contains genes encoding luciferase and green fluorescent protein (GFP) under the control of a cytomegalovirus (CMV) promoter, to allow in vivo tracing and purification after transfection, respectively.…”

Section: Cell Line Transfection and Reagentsmentioning

confidence: 99%

Interplay of VEGFa and MMP2 regulates invasion of glioblastoma

et al. 2014

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Neovascularization plays a substantial role in the regulation of invasion of glioblastoma. However, the underlying molecular basis remains largely unknown. Both vascular endothelial growth factor a (VEGFa) and matrix metalloproteinases 2 (MMP2) are essential for cancer neovascularization and cancer invasion in that they promote endothelial mitogenesis and permeability, and promote extracellular matrix degradation, respectively. In the current study, we found strong positive correlation of VEGFa and phosphorylated MMP2 levels in the glioblastoma from the patients. Thus, we used a human glioblastoma line, A-172, to examine the interaction of VEGFa and MMP2. We found that overexpression of VEGFa in A-172 cells increased MMP2 levels, while inhibition of VEGFa in A-172 cells decreased MMP2 levels. On the other hand, forced changes in MMP2 levels in A-172 cells did not affect VEGFa levels. These data suggest that VEGFa may regulate MMP2 in glioblastoma, while MMP2 did not appear to affect VEGFa levels. We then examined the signaling pathways involved in the regulation of MMP2 levels by VEGFa. Application of a specific extracellular-related kinase 1/2 (ERK1/2) inhibitor, but not application of either an protein kinase B (Akt) inhibitor, or a Jun N-terminal kinase (JNK) inhibitor to VEGFa-overexpressing A-172 cells substantially abolished the effect of VEGFa on MMP2 activation, suggesting that VEGFa may increase MMP2 levels via ERK/mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3-kinase (PI3K) or JNK signaling pathways in glioblastoma. Moreover, adapted VEGFa levels were found to directly and positively affect the glioblastoma development in an intracranial glioblastoma implantation model. Taken together, our data suggest that anti-VEGFa treatment in glioblastoma may inhibit neovascularization not only by VEGFa itself but also by its regulatory effect on MMP2.

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“…В этом процессе участвуют ММП и другие ферменты остеокластов, такие как ММП9 и катепсин К [38][39][40], экспрессия которых по-вышена при РА как в сыворотке крови, так и в суставной жидкости [41][42][43][44][45]. Экспрессия ММП9 активируется про-воспалительными цитокинами, включая ФНОα [46], и способна как снижаться в результате лечения ингибито-рами ФНОα [47,48], так и усиливаться [49].…”

Section: Discussionunclassified

Association of Blood Gene Expressions in Rheumatoid Arthritis Patients With Clinical and Laboratory Parameters Before and After Methotrexate Therapy

Четина¹,

Демидова²,

Каратеев³

et al. 2016

rsp

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Inhibiting effects of Leflunomide metabolite on overexpression of CD147, MMP-2 and MMP-9 in PMA differentiated THP-1 cells

Cited by 19 publications

References 37 publications

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Interplay of VEGFa and MMP2 regulates invasion of glioblastoma

Association of Blood Gene Expressions in Rheumatoid Arthritis Patients With Clinical and Laboratory Parameters Before and After Methotrexate Therapy

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