Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis—A Review

Rohlwink, Ursula K.; Walker, Naomi F.; Ordoñez, Alvaro A.; Li, Yifan J.; Tucker, Elizabeth W.; Elkington, Paul; Wilkinson, Robert J.; Wilkinson, Katalin A.

doi:10.3390/ijms20061350

Cited by 44 publications

(43 citation statements)

References 120 publications

(198 reference statements)

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“…TIMPs are very important factors for TB disease, involved in tissue remodeling and repair upon destruction created by MMPs (17,18). Previous studies have identified MMPs as markers of disease severity, bacterial burdens and as a biomarker for disease in PTB and EPTB (17,(19)(20)(21). Relatively, few studies have focused on examining the circulating levels of MMPs and TIMPs as immune biomarkers in both PTB and EPTB.…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis

et al. 2020

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are potential regulators of tuberculosis (TB) pathology. Whether they are candidates for non-sputum-based biomarkers for pulmonary TB (PTB) and extra-pulmonary TB (EPTB) is not fully understood. Hence, to examine the association of MMPs and TIMPs with PTB and EPTB, we have measured the circulating levels of MMPs 2,3,7,8,9,12, and 13) and TIMPs (TIMP-1, 2, 3, and 4) in PTB, EPTB and compared them with latent tuberculosis (LTB) or healthy control (HC) individuals. We have also assessed their circulating levels before and after the completion of anti-tuberculosis treatment (ATT). Our data describes that systemic levels of 8,9,12 were significantly increased in PTB compared to EPTB, LTB, and HC individuals. In contrast, MMP-7 was significantly reduced in PTB compared to EPTB individuals. Likewise, the systemic levels of MMP-1, 7, 13 were significantly increased in EPTB in comparison to LTB and HC individuals. In contrast, MMP-8 was significantly reduced in EPTB individuals compared to LTB and HC individuals. In addition, the systemic levels of TIMP-1, 2, 3 were significantly diminished and TIMP-4 levels were significantly enhanced in PTB compared to EPTB, LTB, and HC individuals. The circulating levels of TIMP-2 was significantly reduced and TIMP-3 was significantly elevated in EPTB individuals in comparison with LTB and HCs. Some of the MMPs (7,8,9,12, 13 in PTB and 1,7,8, 9 in EPTB) and TIMPs (1, 2, 3, 4 in PTB and 4 in EPTB) were significantly modulated upon treatment completion. ROC analysis showed that MMP-1, 9 and TIMP-2, 4 could clearly discriminate PTB from EPTB, LTB and HCs and MMP-13 and TIMP-2 could clearly discriminate EPTB from LTB and HCs. Additionally, multivariate analysis also indicated that these alterations were independent of age and sex in PTB and EPTB individuals. Therefore, our data demonstrates that MMPs and TIMPs are potential candidates for non-sputum-based biomarkers for differentiating PTB and EPTB from LTB and HC individuals.

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Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis

et al. 2020

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“…Tight junction protein ZO-1 expression was upregulated in TBI mice treated with cordycepin that provided a foundation for cordycepin protecting the structure and function integrity of BBB. MMPs degrades vascular ECM proteins and tight junction proteins, leading to BBB breakdown under pathological conditions [56]. MMP-2 and MMP-9 are the main two MMPs involved in BBB break down and inhibition of the two MMPs contributes to BBB protection [57,58].…”

Section: Discussionmentioning

confidence: 99%

Cordycepin Confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

Wei

Huang

Luo

et al. 2021

Preprint

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Background Traumatic brain injury (TBI) secondary injury, especially white matter injury (WMI), is highly sensitive to neuroinflammation, which further leads to unfavored long-term outcomes. Although the cross-talk between the three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, play a role in the vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract from cordyceps militaris, can inhibit TBI-induced neuroinflammation although the long-term effects of cordycepin remain unknown. Here, we report our investigation of cordycepin’s long-term neuroprotective function and its underlying immunological mechanism. Methods TBI mice model was established with a controlled cortical impact (CCI) method. Cordycepin was intraperitoneally administered twice daily for a week. Neurological outcomes were assessed by behavioral tests, including grid walking test, cylinder test, wire hang test, and rotarod test. Immunofluorescence staining, transmission electron microscopy, and electrophysiology recording were employed to assess histological and functional lesions. Quantitative-PCR and flow cytometry were used to detect neuroinflammation. The tracers of Sulfo-NHS-biotin and Evans blue were assessed for the Blood-brain barrier (BBB) leakage. Western blot and gelatin zymography were used to analyze protein activity or expression. Neutrophil depletion in vivo was performed via using Ly6G antibody intraperitoneal injection. Results Cordycepin administration ameliorated long-term neurological deficits and reduced neuronal tissue loss in TBI mice. Meanwhile, the long-term integrity of white matter was also preserved, which was revealed in multiple dimensions, such as morphology, histology, ultrastructure, and electrical conductivity. Cordycepin administration inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization after TBI. BBB breach was attenuated by cordycepin administration at 3d after TBI. Cordycepin suppressed the activities of MMP-2 and MMP-9 and the neutrophil infiltration at 3d after TBI. Moreover, neutrophil depletion provided a cordycepin-like effect, and cordycepin administration united with neutrophil depletion didn’t show a benefit of superposition. Conclusions The long-term neuroprotective function of cordycepin was via suppressing neutrophil infiltration, thereby preserving BBB integrity and changing microglia/macrophage polarization. These findings provide significant clinical potentials to improve the quality of life for TBI patients.

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“…This may also allow preemptive treatment to reduce morbidity and mortality associated with TB-IRIS. Most efforts to discover predictive markers have focused on immunological aspects of this disease (Chakrabarti et al, 2014; Esmail et al, 2018; George et al, 2017; Narendran et al, 2016; Rateni et al, 2018; Rohlwink et al, 2019; Tan et al, 2015) however, few studies have evaluated the possible metabolic alterations associated with TB-IRIS.…”

Section: Introductionmentioning

confidence: 99%

A pilot metabolomics study of tuberculosis immune reconstitution inflammatory syndrome

Silva

Graham

Webb³

et al. 2019

International Journal of Infectious Diseases

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Background: Diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS. Methods: Plasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window). Molecular features with p < 0.05 and log 2 fold change ≥0.58 were submitted for pathway analysis through MetaboAnalyst. We also elucidated potential metabolic signatures for TB-IRIS using a LASSO regression model. Results: At the study entry, we showed that the arachidonic acid and glycerophospholipid metabolism were altered in the TB-IRIS group. Sphingolipid and linoleic acid metabolism were the most affected pathways during the TB-IRIS window. LASSO modeling selected a set of 8 and 7 molecular features with the potential to predict TB-IRIS at study entry and during the TB-IRIS window, respectively. Conclusion: This study suggests that the use of plasma metabolites may distinguish HIV-TB patients with and without TB-IRIS.

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Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis—A Review

Cited by 44 publications

References 120 publications

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis

Cordycepin Confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

A pilot metabolomics study of tuberculosis immune reconstitution inflammatory syndrome

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