CD147: A Novel Modulator of Inflammatory and Immune Disorders

Zhu, Xiaolei; Song, Zexing; Zhang, S.; Nanda, Anil; Li, G.

doi:10.2174/0929867321666131227163352

Cited by 74 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…leukocytes, platelets, and endothelial cells) that are integrally involved in stroke-induced inflammation and thrombosis. 10 Increased expression of CD147 has been implicated in many human diseases such as cancer, cardiovascular diseases, and neurological disorders. Therapeutic targeting of CD147 has yielded encouraging results in experimental models of human diseases, such as rheumatoid arthritis, asthmatic lung inflammation, myocardial ischemia/reperfusion injury, multiple sclerosis and experimental autoimmune encephalomyelitis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation

Jin

Xiao

Chen

et al. 2017

Stroke

View full text Add to dashboard Cite

Background and Purpose Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147, also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Methods Focal cerebral ischemia was induced in C57BL/6 mice by a 60-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with anti-CD147 function blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24h after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. Results CD147 expression was rapidly increased in ischemic brain endothelium after tMCAO. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after tMCAO. The neuroprotective effects were associated with 1) prevented BBB damage, 2) decreased intravascular fibrin- and platelet- deposition, which in turn reduced thrombosis and increased cerebral perfusion, and 3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced nuclear factor NF-κB activation, matrix metalloproteinase-9 (MMP-9) activity, and plasminogen activator inhibitor-1 (PAI-1) expression in brain microvascular endothelial cells. Conclusions Inhibition of CD147 ameliorates acute ischemic stroke by reducing thrombo-inflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thrombo-inflammatory disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation

Jin

Xiao

Chen

et al. 2017

Stroke

View full text Add to dashboard Cite

show abstract

“…EMMPRIN, also termed CD147 or M6 antigen, is a 58-kDa cell surface glycoprotein described first in tumor cells. It participates in numerous physiological processes, play a central role in tumor metastasis, cell adhesion, angiogenesis, chemoresistance and atherosclerosis [ 1 , 2 ]. EMMPRIN has been reported to stimulates secretion of MMP-9 (matrix metalloproteinase-9) in monocytes [ 1 , 3 ], have strong positive correlation with MMP13 [ 4 , 5 ] or several MMPs in other cells [ 6 , 7 ], and activates MMP-9 in atherosclerotic plaque [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages

et al. 2014

View full text Add to dashboard Cite

In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.

show abstract

“…Cells analyzed for proliferation were pulsed with 3 [H]-thymidine (1 mCi per well) ∼18 h before being harvested and counts per minute (cpm) were measured using a beta counter. The total duration of cells in culture was ∼48 h.…”

Section: T Cell Proliferationmentioning

confidence: 99%

“…EMMPRIN's role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), however, is likely to be through many immunological (1,3) and neural (4) mechanisms apart from affecting MMPs. MS is an immune-mediated disorder of the CNS characterized by the generation of myelin-reactive T cells, demyelination, and axonal degeneration.…”

mentioning

confidence: 99%

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

Hahn

Kaushik

Mishra

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial. We investigated whether and how minocycline affects the expression of EMMPRIN on T cells in culture and in mice afflicted with EAE. EMMPRIN expression in cultures of mouse splenocytes or human PBMCs was elevated upon polyclonal T cell activation, and this was reduced by minocycline correspondent with decreased P-Akt levels. An established MS medication, IFN-β, also diminished EMMPRIN levels on human cells whereas this was not readily observed for fingolimod or monomethylfumarate. In EAE-afflicted mice, minocycline treatment significantly reduced EMMPRIN levels on splenic lymphocytes at the presymptomatic (day 7) phase, and prevented the development of disease. Day 7 spleen transcripts from minocycline-treated EAE mice had a significantly lower MMP-9/TIMP-1 ratio, and significantly lower MCT-1 and CD98 levels, factors associated with EMMPRIN function. Day 16 (peak clinical severity) CNS samples from EAE mice had prominent representation of inflammatory perivascular cuffs, inflammatory molecules and EMMPRIN, and these were abrogated by minocycline. Overall, minocycline attenuated the activation-induced elevation of EMMPRIN on T cells in culture and in EAE mice, correspondent with reduced immune function and EAE CNS pathology.

show abstract

CD147: A Novel Modulator of Inflammatory and Immune Disorders

Cited by 74 publications

References 0 publications

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation

Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

Contact Info

Product

Resources

About