siRNA screening identifies METTL9 as a histidine Nπ-methyltransferase that targets the pro-inflammatory protein S100A9

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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Phagocytosis and activation of bone marrow‐derived macrophages by Plasmodium falciparum gametocytes

Malaria Journal ◽

10.1186/s12936-021-03589-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yolanda Corbett ◽

Silvia Parapini ◽

Federica Perego ◽

Valeria Messina ◽

Serena Delbue ◽

...

Keyword(s):

Nitric Oxide ◽

Bone Marrow ◽

Plasmodium Falciparum ◽

Innate Immune ◽

Innate Immune Responses ◽

Murine Bone Marrow ◽

Inflammatory Protein ◽

Life Cycle Stages ◽

Cytokine Levels ◽

Necrosis Factor

Abstract Background The innate immune response against various life cycle stages of the malaria parasite plays an important role in protection against the disease and regulation of its severity. Phagocytosis of asexual erythrocytic stages is well documented, but little and contrasting results are available about phagocytic clearance of sexual stages, the gametocytes, which are responsible for the transmission of the parasites from humans to mosquitoes. Similarly, activation of host macrophages by gametocytes has not yet been carefully addressed. Methods Phagocytosis of early or late Plasmodium falciparum gametocytes was evaluated through methanol fixed cytospin preparations of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated for 2 h with P. falciparum and stained with Giemsa, and it was confirmed through a standardized bioluminescent method using the transgenic P. falciparum 3D7elo1-pfs16-CBG99 strain. Activation was evaluated by measuring nitric oxide or cytokine levels in the supernatants of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated with early or late gametocytes. Results The results showed that murine bone marrow-derived macrophages can phagocytose both early and late gametocytes, but only the latter were able to induce the production of inflammatory mediators, specifically nitric oxide and the cytokines tumour necrosis factor and macrophage inflammatory protein 2. Conclusions These results support the hypothesis that developing gametocytes interact in different ways with innate immune cells of the host. Moreover, the present study proposes that early and late gametocytes act differently as targets for innate immune responses.

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Generation of Monoclonal Antibodies for Sensitive Detection of Pro-Inflammatory Protein S100A9

Applied Sciences ◽

10.3390/app11104659 ◽

2021 ◽

Vol 11 (10) ◽

pp. 4659

Author(s):

Eun-Jung Kim ◽

Gyu-Min Im ◽

Chang-Soo Lee ◽

Yun-Gon Kim ◽

Byoung Joon Ko ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Calcium Binding ◽

Nucleotide Sequences ◽

Antibody Fragments ◽

High Yield ◽

Antigen Binding ◽

Hybridoma Cell Culture ◽

Inflammatory Protein ◽

Inflammatory Processes ◽

Yield And Purity

The calcium-binding protein S100A9 regulates inflammatory processes and the immune response. It is overexpressed in a variety of inflammatory and oncologic conditions. In this study, we produced a recombinant human S100A9 (hS100A9) antigen with high yield and purity and used it to generate a hybridoma cell culture-based monoclonal anti-hS100A9 antibody. We selected five anti-hS100A9 antibodies from cell supernatants that showed high antigen binding efficiency and identified the nucleotide sequences of three antibodies: two with high effective concentration values and one with the lowest value. The antigen and antibody development procedures described herein are useful for producing large amounts of monoclonal antibodies against hS100A9 and other antigens of interest. The nucleotide sequences of the anti-hS100A9 monoclonal antibody revealed herein will be helpful in the generation of recombinant antibodies or antibody fragments against hS100A9.

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Anti-NLRP3 Inflammasome Natural Compounds: An Update

Biomedicines ◽

10.3390/biomedicines9020136 ◽

2021 ◽

Vol 9 (2) ◽

pp. 136

Author(s):

Baolong Liu ◽

Jiujiu Yu

Keyword(s):

Nlrp3 Inflammasome ◽

Protein Complex ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Natural Compounds ◽

Pyrin Domain ◽

Inflammatory Protein ◽

Wide Range ◽

Activation Mechanisms ◽

Stress Signals

The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. This pro-inflammatory protein complex plays critical roles in pathogenesis of a wide range of diseases including neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Therefore, intensive efforts have been devoted to understanding its activation mechanisms and to searching for its specific inhibitors. Approximately forty natural compounds with anti-NLRP3 inflammasome properties have been identified. Here, we provide an update about new natural compounds that have been identified within the last three years to inhibit the NLRP3 inflammasome and offer an overview of the underlying molecular mechanisms of their anti-NLRP3 inflammasome activities.

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Serum levels of macrophage inflammatory protein-1 alpha (MIP-1α) correlate with the extent of bone disease and survival in patients with multiple myeloma

British Journal of Haematology ◽

10.1046/j.1365-2141.2003.04561.x ◽

2003 ◽

Vol 123 (1) ◽

pp. 106-109 ◽

Cited By ~ 114

Author(s):

Evangelos Terpos ◽

Marianna Politou ◽

Richard Szydlo ◽

John M. Goldman ◽

Jane F. Apperley ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Disease ◽

Serum Levels ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

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A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques

Scientific Reports ◽

10.1038/s41598-020-79427-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kun Luo ◽

James T. Gordy ◽

Fidel Zavala ◽

Richard B. Markham

Keyword(s):

San Diego ◽

Severe Disease ◽

Antibody Responses ◽

Poly I:C ◽

Protein Vaccine ◽

Primate Model ◽

Polyinosinic:Polycytidylic Acid ◽

Inflammatory Protein ◽

Immature Dendritic Cells ◽

High Concentrations

AbstractInfants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system. In the current study, a squalene based adjuvant (AddaVax, InvivoGen, San Diego, Ca) equivalent to the clinically approved MF59 (Seqiris, Maidenhead, UK) elicited greater antibody responses in mice than the previously employed adjuvant polyinosinic:polycytidylic acid, ((poly(I:C), InvivoGen, San Diego, Ca) and the clinically approved Aluminum hydroxide gel (Alum, Invivogen, San Diego, Ca) adjuvant. Use of the AddaVax adjuvant also expanded the range of IgG subtypes elicited by mouse vaccination. Sera passively transferred into mice from MCSP/AddaVax immunized 1 and 6 month old macaques significantly reduced liver sporozoite load upon sporozoite challenge. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization. The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population.

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