MMP-mediated cleavage of β-dystroglycan in myelin sheath is involved in autoimmune neuritis

Zhao, Xinyu; Li, Guo Zhong; Sun, Bo; Zhang, Zhong Ling; Yin, Yan; Tian, Yu; Li, He; Li, Hu Lun; Wang, De Sheng; Zhong, Di

doi:10.1016/j.bbrc.2010.01.062

Cited by 20 publications

(19 citation statements)

References 30 publications

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“…Previous studies have shown a link between increased levels of MMPs and autoimmunity in humans, but these reports did not provide direct evidence for a causative role for these proteins in the development and/or maintenance of autoimmune diseases. However, in an animal Guillain-Barré syndrome model with increased MMP2 and MMP9 levels, inhibition of these MMPs with captopril reduced demyelination and inflammatory cell infiltration, and gave disease improvement [25]. Similar results were found for experimental autoimmune encephalomyelitis [26].…”

Section: Discussionsupporting

confidence: 64%

Matrix Metalloproteinases in Myasthenia Gravis

Helgeland

Petzold²,

Luckman³

et al. 2011

Eur Neurol

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Introduction: Myasthenia gravis (MG) is an autoimmune disease with weakness in striated musculature due to anti-acetylcholine receptor (AChR) antibodies or muscle specific kinase at the neuromuscular junction. A subgroup of patients has periocular symptoms only; ocular MG (OMG). Matrix metalloproteinases (MMP) are increased in several autoimmune diseases, including generalized MG (GMG), and have been suggested to play a role in immune cell infiltration, basement membrane breakdown and autoimmune pathogenesis. Methods: Total levels of MMP2, MMP3 and MMP9 were measured in serum by ELISA. Results: The MG patients had increased serum levels of MMP2 (median values 200.7 vs. 159.7 ng/ml, p < 0.001) and MMP9 (median values 629.6 vs. 386.4 ng/ml, p < 0.001) compared to controls. A subgroup of patients had increased MMP3 concentration (p = 0.001). The differences were not dependent on presence of AChR antibodies. No difference was observed between GMG and OMG patients with regard to MMP2 (p = 0.598), MMP3 (p = 0.450) and MMP9 (p = 0.271). Discussion: The increased MMP levels in our MG patients group and the lack of dependence on anti-AChR antibodies suggest that MMP2, MMP3 and MMP9 play a role in the development of MG. The similarities between GMG and OMG support OMG as a systemic disease.

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Section: Discussionsupporting

confidence: 64%

Matrix Metalloproteinases in Myasthenia Gravis

Helgeland

Petzold²,

Luckman³

et al. 2011

Eur Neurol

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“…We did not found any significant changes of MMP-2 expression during the course of EAN, which is in accordance with earlier reports that MMP-2 usually showed a constitutively expression during the pathological processes [20,21]. Our previous study has found that cleavage of dystroglycan complex of Schwann cells mediated by MMP-9 caused inflammatory demyelination in autoimmune neuritis [22]. Here, we found that the expression of MMP-9 was in positive correlation with disease severity (Fig.…”

Section: Discussionsupporting

confidence: 95%

“…Therefore, inhibition of p38 MAPK declined the MMP-9 level, and relieved pathological changes and clinical signs. Our previous report showed that MMP-9 inhibitor, captopril can improve clinical signs and pathological changes in EAN [22]. Thus, drugs which targeting MMP-9 and upstream signaling molecules (i.e.…”

Section: Discussionmentioning

confidence: 98%

Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9, and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in Rats

Sun

Chen

et al. 2015

Neurochem Res

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Dysfunctional expression of matrix metalloproteinase-9 (MMP-9) has been found to be closely associated with the experimental autoimmune neuritis (EAN). In this study, we explored the role of p38 mitogen-activated protein kinases (p38 MAPK) in the regulation of MMP-9 in sciatic nerves of EAN rats. We analyzed the expression changes of MMP-2, MMP-3, MMP-9, and mitogen-activated protein kinases (MAP kinases) in sciatic nerves of EAN rats and investigated the effect of p38 MAPK inhibitor (SB203580) on MMP-9 expression and pathological changes in EAN. Real-time PCR and western blot analyses showed that the expression of MMP-2 exhibited no significant changes throughout the course of EAN, while MMP-3 and MMP-9 presented the relatively increased expression compared with that in control group. MAP kinases, including p38 MAPK, ERK1/2, and JNK1/2, were activated in the sciatic nerve of EAN rats, and phosphorylated p38 MAPK showed similar patterns of expression to MMP-9. The expression of MMP-9 and phosphorylated p38 MAPK in sciatic nerves were in positive correlation with disease severity. In addition, SB203580 treatment significantly reduced the mRNA and protein level of MMP-9 in sciatic nerves on the peak phase of EAN. Inhibition of p38 MAPK also relieved neurologic severity and ameliorated pathological changes in EAN. In conclusion, SB203580 may ameliorate clinical deficit and pathological changes in EAN by reducing the MMP-9 expression in sciatic nerves, which suggest that p38 MAPK inhibitor such as SB203580 could be considered as a therapeutic candidate in autoimmune neuropathies.

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“…NF-jB augments the expression of adhesion molecules, such as intercellular adhesion molecule 1, vascular-cell adhesion molecule 1, and E-selectin [23], and is thereby instrumental in the recruitment of leukocytes from the circulation to the site of inflammation. Moreover, NF-jB regulates the expression of matrix metalloproteinases [24], which facilitates the migration of these cells through the blood-nerve barrier [25]. Recent studies have shown that MAPK are important mediators to regulate the NF-jB-dependent gene expression in various cell types.…”

Section: Discussionmentioning

confidence: 99%

TNF-α Expression in Schwann Cells is Induced by LPS and NF-κB-Dependent Pathways

et al. 2012

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Lipopolysaccharide (LPS) is recognized by Toll-like receptor 4 and activates mitogen-activated protein kinase, which leads to the induction of proinflammatory cytokine gene expression. In vivo, Schwann cells (SCs) at the site of injury may also produce tumor necrosis factor-α (TNF-α). However, the precise mechanism that regulates TNF-α synthesis is still not clear. The nuclear transcription factor-κB (NF-κB) is an important transcription factor which is involved in the regulation of host immune responses. In the present study, we found that LPS possessed a comparable specific activity for activation of NF-κB-dependent gene expression in SCs. We also observed IκB-α/IκB-β degradation and the nuclear translocation of P65 due to LPS treatments. LPS-elicited TNF-α production in SCs was also drastically suppressed by SN50 (NF-κB inhibitor).

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MMP-mediated cleavage of β-dystroglycan in myelin sheath is involved in autoimmune neuritis

Cited by 20 publications

References 30 publications

Matrix Metalloproteinases in Myasthenia Gravis

Matrix Metalloproteinases in Myasthenia Gravis

Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9, and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in Rats

TNF-α Expression in Schwann Cells is Induced by LPS and NF-κB-Dependent Pathways

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