Matrix metalloproteinase- 9 (MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) as non-invasive biomarkers of remodelling in asthma

Hassan, Neveen; Mohamed-Hussein, Aliae; Mohamed, Ebtssam; Mohamed, Omnia; Mohamed, Hanan A.; Tammam, Manal

doi:10.1183/13993003.congress-2015.oa1467

Cited by 3 publications

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“…Therefore, the dysregulations of MMP9 systems (gene expressions, post-translational modifications, levels of activators vs. inhibitors) lead to the development of pathological conditions [ 46 , 47 ]. The low level of TIMP1 and persistent MMP9 activity in neutrophils which bring about airway remodelling and congestion in association with the acute inflammatory responses are implicated in development of both ARDS and acute asthma [ [48] , [49] , [50] , [51] ]. Recently the gene expressions of TIMP1 in the bronchoalveolar lavage fluid of COVID-19 patients have been found to undergo upregulation in one victim and downregulation in another one as well as upregulation in the blood mononuclear cells of the other three victims [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

et al. 2020

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Aims The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. Materials and methods The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. Key findings A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. Significance The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

et al. 2020

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“…IL‐8 (chemokine for neutrophils) was reported to activate airways neutrophils and induce neutrophil extracellular trap (NET) release, contributing to AEC damage and lung function decline 32 . MMP‐9 and TIMP‐1 are known as major cytokines involved in airways remodelling 23 . Moreover, CC16 treatment could suppress the Der p1‐induced IL‐8, MMP‐9 and TIMP‐1 production and fibronectin expression, and restore the disrupted tight junction proteins in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-9, TIMP-1, periostin and TGF-β1 are known to contribute to airways remodelling. [20][21][22][23] When compared between the present BDR and absent BDR groups, significantly higher levels of serum MMP-9 (507.8 ± 259.5 vs. 352.2 ± 240.9 ng/mL, p = .019) and MPO (560.9 ± 234.0 vs. 412.3 ± 242.8 ng/mL, p = .022) were noted (Table 2); however, no significant differences were noted in serum predicted the present BDR group from the absent BDR group (area under the curve [AUC] = 0.740, p = 0.004, Figure 1D).…”

Section: Comparison Of Serum Biomarkersmentioning

confidence: 99%

Role of club cell 16‐kDa secretory protein in asthmatic airways

Jung

Cao

Quoc

et al. 2023

Clin Experimental Allergy

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Background Club cell 16‐kDa secretory protein (CC16) is a pneumoprotein and functions as an anti‐inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on airways inflammation have not been fully evaluated. Methods We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time‐dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested. Results Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV1% (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV1% and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP‐9 and TIMP‐1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone). Conclusion Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.

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Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma

et al. 2021

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Background: Asthma is a heterogeneous syndrome with a broad clinical spectrum and high drug response variability. The inflammatory response in asthma involves multiple effector cells and mediator molecules. Based on asthma immunopathogenesis, precision medicine can be a promising strategy for identifying biomarkers. Biologic therapies acting on the IL-5/IL-5 receptor axis have been developed. IL-5 promotes proliferation, differentiation and activation of eosinophils by binding to the IL-5 receptor, located on the surface of eosinophils and basophils. This study aimed to investigate the expression of IL5RA in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha.Methods: Sixty peripheral blood samples, 30 from healthy controls and 30 from asthmatic patients, were selected for a transcriptomic RNAseq study. Differential expression analysis was performed by statistical assessment of fold changes and P-values. A validation study of IL5RA expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on IL5RA expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The IL5RA mRNA levels were normalized to GAPDH and TBP expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines.Results:IL5RA was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients (P = 8.63E-08 and fold change of 2.22). In the qPCR validation study, IL5RA expression levels were significantly higher in asthmatic patients than in controls (P < 0.001). Significant expression differences were present in different asthmatic types. In the biological drug study, patients treated with benralizumab showed a significant decrease in IL5RA expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients.Conclusions: These results indicate that IL5RA is overexpressed in patients with different types of asthma. It could help identify which asthmatic patients will respond more efficiently to benralizumab, moving toward a more personalized asthma management. Although further studies are required, IL5RA could play a role as a biomarker and pharmacogenetic factor in asthma.

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Matrix metalloproteinase- 9 (MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) as non-invasive biomarkers of remodelling in asthma

Cited by 3 publications

References 0 publications

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

Role of club cell 16‐kDa secretory protein in asthmatic airways

Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma

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