Nuclear Factor κB Activation Pathways During  Infection

Andrade, Bruno B.; Amaral, Eduardo Tadeu Roque

doi:10.1177/1179568917695833

Cited by 2 publications

(2 citation statements)

References 131 publications

(164 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…99 NF-κB orchestrates the transcription of numerous critical genes allied with antimycobacterial defense mechanisms in TB. 100,101 The regulatory mechanisms of NF-κB triggered by TNF-α and its impact on MMP expression and their endogenous inhibitors (TIMPs) have been investigated. NF-κB seems to be engaged in the intricate control of equilibrium between MMPs and TIMPs.…”

Section: ■ Nf-κb Regulation In Mmpmentioning

confidence: 99%

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Jhilta,

Jadhav,

Singh

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtbassociated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.

show abstract

Section: ■ Nf-κb Regulation In Mmpmentioning

confidence: 99%

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Jhilta,

Jadhav,

Singh

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…Mtb infection-induced AKT phosphorylation (5 min) at a very early time point and was evident till 120 min (Figure 5a,b). Growing evidence of NF-κβ activation post Mtb infection [31,32], drove us to examine the status of the activation of this transcription factor. We noticed that activation of NF-κβ is comparatively a later event (peak at 120 min) than that of AKT (Figure 5a; lower panel and b) while, NF-κβ activation is inhibited by inhibition of AKT (by AKT siRNA), NF-κβ inhibitor did not have any effect on AKT activation (Figure 5c,d).…”

Section: Increased Exosome Release By +M Macrophages Involves Akt Pho...mentioning

confidence: 99%

Elucidation of the signalling pathways for enhanced exosome release from Mycobacterium‐infected macrophages and subsequent induction of differentiation

et al. 2022

View full text Add to dashboard Cite

Exosomes are extracellular vesicles released by all cell types; perform several important functions such as cell-to-cell communication, growth, differentiation and so on. Exosomes elicit several signalling mechanisms as they carry information in the form of DNA, RNA or protein docked on them. We show that exosomes released from Mycobacterium tuberculosis (Mtb)-infected macrophages not only induce differentiation of naïve monocytes but also generate functionally active macrophages via MAPK-dependent signalling mechanism through MK-2 and NF-κβ activation which is completely different from the differentiation induced by exosomes from uninfected macrophages. Further, we elucidate unequivocally the signalling mechanism behind the enhanced release of exosome generation from infected macrophages driven by AKT phosphorylation involving Rab7a and Rab11a. Genes of both ESCRT-dependent and -independent pathways are found to be involved in enhanced exosomes release and are modulated by AKT. However, interestingly, the genes of the ESCRT-independent pathway are dependent on NF-κβ activation while the genes of the dependent pathway are not, suggesting two parallel signalling cascades operating in tandem.

show abstract

Nuclear Factor κB Activation Pathways During Infection

Cited by 2 publications

References 131 publications

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Elucidation of the signalling pathways for enhanced exosome release from Mycobacterium‐infected macrophages and subsequent induction of differentiation

Contact Info

Product

Resources

About