Neutralization of MMP-2 protects Staphylococcus aureus infection induced septic arthritis in mice and regulates the levels of cytokines

Sultana, Sahin; Adhikary, Rana; Nandi, Ajeya; Bishayi, Biswadev

doi:10.1016/j.micpath.2016.08.021

Cited by 13 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports demonstrated the clinical benefits of antibiotic and TNF-α inhibitor combination therapies relating to both arthritis severity and bone destruction in addition to reductions in the mortality rate by a combination therapy in experimental S. aureus –induced septic arthritis [55]. Recently we have observed that certain interaction exists between TNF-α and MMP-2 during the course of septic arthritis in S. aureus infected mice, hence further experiments are warranted to figure out the impact of TNF-α on MMP-2 activation via receptors for TNF-α (TNFR-I and TNFR-II) during S. aureus induced septic arthritis [56]. …”

Section: Discussionmentioning

confidence: 99%

Riboflavin along with antibiotics balances reactive oxygen species and inflammatory cytokines and controls Staphylococcus aureus infection by boosting murine macrophage function and regulates inflammation

Dey

Bishayi

2016

J Inflamm

Self Cite

View full text Add to dashboard Cite

BackgroundMacrophages serve as intracellular reservoirs of S. aureus. Recent in vitro studies have confirmed high level resistance by S. aureus to macrophage mediated killing and the intracellular persistence of Staphylococci may play an important role in the pathogenesis. Since this localization protects them from both cell-mediated and humoral immune responses, therefore, a successful anti-staphylococcal therapy should include the elimination of intracellular bacteria, further protecting the host cells from staphylococci-induced cell death. So, only antibiotic therapy may not be helpful, successful therapy needs combination of drugs not only for elimination of pathogen but also for rescuing the host cell for S. aureus induced cell death.MethodsIn keeping with this idea an in vitro study has been done to examine the effect of Riboflavin along with antibiotics on phagocytosis, hydorgen peroxide, superoxide production, antioxidant enzyme levels, and cytokine levels in mouse macrophages for amelioration of the Staphylococcus aureus burden. The immune boosting effects of Riboflavin have been validated through perturbations of redox homeostasis and pro-inflammatory cytokines measurements.ResultsIt was observed that the supplementation of Vitamin B-2 (Riboflavin) not only enhances macrophage function as previously reported but also decreases pro-inflammatory responses in Staphylococcus aureus infected macrophages. The observed influence of Riboflavin on enhanced antimicrobial effects such as enhanced phagocytosis of macrophages exposed to S. aureus, hydrogen peroxide or superoxide production when combined with either ciprofloxacin (CIP) or Azithromycin (AZM) and decrease in pro-inflammatory responses of IFN-γ, IL-6, IL-1β. Riboflavin treatment also decreased NO and TNF-α level possibly by inhibiting the NF-κβ pathway. The increased antioxidant enzymes like glutathione reductase, SOD and GSH level helped in maintaining a stable redox state in the cell.ConclusionRiboflavin plus antibiotic pretreatment not only enhances macrophage functions but also decreases proinflammatory responses in Staphylococcus aureus infected macrophages indicating better bacterial clearance and regulated inflammation which may be considered as a novel and important therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Riboflavin along with antibiotics balances reactive oxygen species and inflammatory cytokines and controls Staphylococcus aureus infection by boosting murine macrophage function and regulates inflammation

Dey

Bishayi

2016

J Inflamm

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a murine model of Staphylococcus aureus -induced septic arthritis it was demonstrated that the inhibition of MMP-2 activity resulted in significantly decreased serum levels of the pro inflammatory cytokines TNFα, IL-1β, IL-6, IL-12, IFN-γ and increased levels of the anti-inflammatory cytokine IL-10 [69]. This evidence emphasizes that the regulatory roles of MMPs can lead to profound effects that tilt the balance towards resolution or perpetuation of the inflammatory response, and that these changes are strong enough to be reflected in serum levels of inflammatory biomarkers.…”

Section: Mmp-mediated Regulation Of Inflammatory Responsementioning

confidence: 99%

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

Cavalla

Patricia

Sorsa

et al. 2017

IJMS

214

188

View full text Add to dashboard Cite

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.

show abstract

“…Bacterial products of Staphylococcus aureus, which grows primarily in the extracellular bone microenvironment and forms biofilms, induce an inflammatory response. Factors released by cells adjacent to bacteria include TNF-α, IL-1β, IL-6, IFN-γ, and IL-12 as well as the chemokines CCL3 (also known as MIP1α), CXCL1, CXCL2 (also known as MIP2α), and CXCL8 (150)(151)(152)(153)(154). Further linking mechanisms of bone loss in infectious and non-infectious inflammatory states, the NLRP3 inflammasome is implicated in the response of innate immune cells to Staphylococcus aureus infection.…”

Section: Infection-associated Osteolysismentioning

confidence: 99%