Purification of truncated and mutated Chemotaxis Inhibitory Protein of Staphylococcus aureus—an anti-inflammatory protein

ABSTRACTBacterial pathogens have evolved to secrete strong anti-inflammatory proteins that target the immune system. It was long speculated whether these virulence factors could serve as therapeutics in diseases in which abnormal immune activation plays a role. We adopted the secreted chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) as a model virulence factor-based therapeutic agent for diseases in which C5AR1 stimulation plays an important role. We show that the administration of CHIPS in human C5AR1 knock-in mice successfully dampens C5a-mediated neutrophil migration during immune complex-initiated inflammation. Subsequent CHIPS toxicology studies in animal models were promising. However, during a small phase I trial, healthy human volunteers showed adverse effects directly after CHIPS administration. Subjects showed clinical signs of anaphylaxis with mild leukocytopenia and increased C-reactive protein concentrations, which are possibly related to the presence of relatively high circulating anti-CHIPS antibodies and suggest an inflammatory response. Even though our data in mice show CHIPS as a potential anti-inflammatory agent, safety issues in human subjects temper the use of CHIPS in its current form as a therapeutic candidate. The use of staphylococcal proteins, or other bacterial proteins, as therapeutics or immune-modulators in humans is severely hampered by pre-existing circulating antibodies.

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Faculty Opinions recommendation of Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009346.124407 ◽

2002 ◽

Author(s):

Giorgio Berton

Keyword(s):

Staphylococcus Aureus ◽

Inflammatory Factor ◽

Anti Inflammatory

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Faculty Opinions recommendation of Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9573956.10235054 ◽

2011 ◽

Author(s):

Scheffer Chuei-Goong Tseng

Keyword(s):

Mechanical Injury ◽

Inflammatory Damage ◽

Inflammatory Protein ◽

Anti Inflammatory

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Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22020488 ◽

2021 ◽

Vol 22 (2) ◽

pp. 488

Author(s):

Young-Su Yi

Keyword(s):

Rheumatic Diseases ◽

Fruits And Vegetables ◽

Inflammatory Responses ◽

Protein Complexes ◽

Cellular Damage ◽

Inflammatory Rheumatic Diseases ◽

Inflammasome Activation ◽

Central Feature ◽

Inflammatory Protein ◽

Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

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Azadirachta indica A. Juss (Neem) oil topical formulation with liquid crystals ensconcing depot water for anti-inflammatory, wound healing and anti-methicillin resistant Staphylococcus aureus activities

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102563 ◽

2021 ◽

pp. 102563

Author(s):

Kaushita Banerjee ◽

Monami Chatterjee ◽

Rajendra Sandur V ◽

Ramesh Nachimuthu ◽

Harishkumar Madhyastha ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Wound Healing ◽

Liquid Crystals ◽

Azadirachta Indica ◽

Methicillin Resistant Staphylococcus Aureus ◽

Neem Oil ◽

Topical Formulation ◽

Methicillin Resistant ◽

Anti Inflammatory

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The Antimicrobial and Anti-Inflammatory Effects of Silver Nanoparticles Synthesised from Cotyledon orbiculata Aqueous Extract

Nanomaterials ◽

10.3390/nano11051343 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1343

Author(s):

Caroline Tyavambiza ◽

Abdulrahman Mohammed Elbagory ◽

Abram Madimabe Madiehe ◽

Mervin Meyer ◽

Samantha Meyer

Keyword(s):

Staphylococcus Aureus ◽

Silver Nanoparticles ◽

Metallic Nanoparticles ◽

Methicillin Resistance ◽

Antimicrobial Activities ◽

Transmission Electron ◽

Anti Inflammatory ◽

Anti Inflammation ◽

Important Medicinal Plant ◽

Pro Inflammatory Cytokines

Cotyledon orbiculata, commonly known as pig’s ear, is an important medicinal plant of South Africa. It is used in traditional medicine to treat many ailments, including skin eruptions, abscesses, inflammation, boils and acne. Many plants have been used to synthesize metallic nanoparticles, particularly silver nanoparticles (AgNPs). However, the synthesis of AgNPs from C. orbiculata has never been reported before. The aim of this study was to synthesize AgNPs using C. orbiculata and evaluate their antimicrobial and immunomodulatory properties. AgNPs were synthesized and characterized using Ultraviolet-Visible Spectroscopy (UV-Vis), Dynamic Light Scattering (DLS) and High-Resolution Transmission Electron Microscopy (HR-TEM). The antimicrobial activities of the nanoparticles against skin pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Methicillin Resistance Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans) as well as their effects on cytokine production in macrophages (differentiated from THP-1 cells) were evaluated. The AgNPs from C. orbiculata exhibited antimicrobial activity, with the highest activity observed against P. aeruginosa (5 µg/mL). The AgNPs also showed anti-inflammatory activity by inhibiting the secretion of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1 beta) in lipopolysaccharide-treated macrophages. This concludes that the AgNPs produced from C. orbiculata possess antimicrobial and anti-inflammation properties.

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