Petya Dimitrova

The Stephan Angeloff Institute of Microbiology · Department of Immunology

The current study aimed to investigate exopolysaccharides (EPSs) produced by two Antarctic yeasts isolated from soil and penguin feathers samples collected on Livingston Island (Antarctica). The strains were identified as belonging to the species Leucosporidium yakuticum (LY) and Cystobasidium ongulense (CO) based on molecular genetic analysis. The...

Human γδ T cells are enriched at the maternal-fetal interface (MFI, decidua basalis) showing a highly differentiated phenotype. However, their functional potential is not well-known and it is not clear whether this decidua-enrichment is associated with specific γδ T cell receptors (TCR) as is observed in mice. Here we addressed these open questions...

The current study aimed to investigate exopolysaccharides (EPSs) produced by two Antarctic yeasts isolated from soil and penguin feathers samples collected on Livingston Island (Antarctica). The strains were identified as belonging to the species Leucosporidium yakuticum (LY) and Cystobasidium ongulense (CO) based on a molecular genetic analysis. T...

Previous studies have shown that polyreactive antibodies play an important role in the frontline defense against the dissemination of pathogens in the pre-immune host. Interestingly, antigen-binding polyreactivity can not only be inherent, but also acquired post-translationally. The ability of individual monoclonal IgG and IgE antibodies to acquire...

Introduction: As has been shown previously, various protein-modifying agents can change the antigen-binding properties of immunoglobulins. However, induced polyspecificity of human secretory immunoglobulin A (sIgA) has not been previously characterized in detail. Methods: In the present study, human secretory immunoglobulin A (IgA) was exposed t...

Recent studies have shown that polyspecific antibodies play an important role in the frontline defense against the dissemination of pathogens in the pre-immune host. Interestingly, antigen-binding polyspecificity can not only be inherent, but also acquired post-translationally. The ability of individual monoclonal IgE and IgG antibodies to acquire...

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that mi...

Plants from the Veronica genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated Veronica austriaca L., collected from two habitats in Bulgaria-the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), were analyzed by nuclear magnetic resonance (NMR) spectrosco...

Among responders to microbial invasion, neutrophils represent one of the earliest and perhaps most important factors that contribute to initial host defense. Effective neutrophil immunity requires their rapid mobilization to the site of infection, which requires efficient extravasation, activation, chemotaxis, phagocytosis, and eventual killing of...

Background: Neutrophils have a short live in circulation and accelerate greatly local immune responses via increased granulopoiesis and migration at high numbers to infected or inflamed tissue. Hypothesis: Since neutrophils produce a variety of factors with destructive and pro- inflammatory potential the regulation of their homeostasis and functio...

: Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in...

Clinopodium vulgare L. (wild basil) has a wide range of ethnopharmacological applications and accumulates a broad spectrum of phenolic compounds, recognized for their anti-inflammatory and anticancer properties. The triggered cyclooxygenase-2 (COX-2) expression is creating an immunosuppressive microenvironment in the inflamed tissue and considered...

The Verbascum species are widely used traditional herb remedies against respiratory, inflammatory conditions and disorders. In the present study methanol extract of the aerial parts of the endemic Verbascum nobile Velen, was investigated and two novel iridoid glycosides 1 and 2, together with nine known constituents: iridoids, phenylethanoids, and...

Osteoarthritis (OA) is an age-related joint degenerative disease associated with pain, joint deformity and disability. The disease starts with cartilage damage but then progressively involves subchondral bone causing an imbalance between osteoclast-driven bone resorption and osteoblasts-driven remodeling. Herein we summarize the data for the role o...

Intravenous immunoglobulin (IVIG) are purified IgG preparations made from the pooled plasma from thousands of healthy donors and are being tested in preclinical mouse models. Inherent challenges, however, are the pluripotency of IVIG and its xenogeneicity in animals. IVIG can alter the viability of human neutrophils via agonistic antibodies to Fas...

Rhodiola rosea L. extracts have shown neuroprotective, anti-fatigue, anti-inflammatory and antitumor properties. However, the studies on their effect on T cell function are rather scarce. We examined the potential of R. rosea extract and its major constituents – salidroside, rosarin, rosavin and rosin to alter cell growth of human Jurkat T cells, a...

Several immune cell populations are involved in cartilage damage, bone erosion, and resorption processes during osteoarthritis. The purpose of this study was to investigate the role of NK cells in the pathogenesis of experimental osteoarthritis and whether and how neutrophils can regulate their synovial localization in the disease. Experimental ost...

Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single pro-inflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could well be explained by the widespread gene expression dysregulation known as "genomic storm" in these...

Neutrophils are activated at early stages of innate immune response. Our previous investigations have shown that neutrophils express RANKL and produce IL-17 and IFN-γcontributing to activation of osteoclasts, joint degeneration and destruction in arthritis. Activation and migration of neutrophils can be regulated by protein kinase C (PKC). He...

The development of inflammatory immune response is related to an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) signaling. The intracellular molecules from this pathway are sensitive to the alterations in the microenvironment. The changes in cellular redox state, proliferation, gene expression pattern and genom...

Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA). Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administr...

We investigated the effect of interleukin (IL)-17 on Ly6G+ cell apoptosis in zymosan-induced arthritis (ZIA) and oedema (ZIO). Zymosan injection at the ankle joint caused swelling and coincided with histological joint alterations and IL-17A expression in areas with cell infiltrates. Flow cytometry of blood demonstrated increased frequencies of Ly6G...

Neutrophils are innate immune cells involved in the initial inflammatory response and in the pathogenesis of rheumatoid arthritis (RA), an inflammatory joint disease. They produce cytokines, chemokines, proinflammatory mediators and secrete enzymes causing a direct destruction of cartilage and bone. Herein we investigated the ability of neutrophils...

The janus kinase (JAK)-signal transducer and activator of transcription (STAT) cascade plays a principal role in the signaling of a vast array of cytokines and growth factors which stimulates diverse cellular functions and immune responses. Osteoarthritis (OA) is the most common joint disease in the adult population. The present study was designed...

Recently, protein kinase inhibitors are used to limit the uncontrolled immune responses in cancer and autoimmune diseases. Tyrphostin AG-490 is a novel benzylidine malononitrile analogue that inhibits the activity of Janus activation kinase 2 (JAK2). In the present study we investigate the effect of the drug on the development of aseptic shock. The...

Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause severe infectious disease in human, were used to infect properdin-deficient and wildtype mice. The aim was to deduce a role for properdin, positive regulator of the alternative pathway of complement activation, by comparing and contrasting the immune response of the two...

We investigated the ability of neutrophils to express receptor activator of nuclear factor kappa-B ligand (RANKL), to secrete osteoprotegerin (OPG), and to produce IL-17. Arthritis was induced by intra-articular injection of zymosan, a ligand for Toll-like receptor 2 (TLR2). Frequencies of neutrophils in bone marrow (BM), blood and synovial fluid (...

Tyrphostin AG490 is a Janus kinase (JAK) 2 inhibitor that is clinically used as an anticancer agent and is also effective in various models of inflammatory and autoimmune diseases. In this study, we examined the effects of tyrphostin AG490 on the development of collagenase-induced osteoarthritis (CIOA). Our results showed that tyrphostin-ameliorate...

We read with great interest the recent paper by Azmi et al. [1][1] who reported the in vitro and in vivo anti-lymphoma activity of novel specific inhibitors of nuclear export (SINE). The authors focused on targeting a main nuclear export protein called chromosome maintenance region 1 (CRM1) or

Introduction Protein kinases regulate the expression of many genes that are pivotal for inflammation. This review aims to summarise data on a group of small molecules capable to inhibit tyrosine kinases (TYKs), named tyrphostins. They are derivatives of benzylidenemalonitrile that decrease tyrosine phosphorylation, thereby affecting not a single me...

Verbascum species are widely used in folk medicine because of their broad range of biological activities. Harpagoside, an iridoid glycoside isolated from some Verbascum plants is known for its anti-inflammatory properties. In the present study, the effect of five extracts of Verbascum species and harpagosides were evaluated in mouse models of acute...

Zymosan-induced arthritis is an experimental model of rheumatoid arthritis used for analyzing cells and molecules that mediate the pathogenesis of inflammatory joint diseases. Although, the alternative pathway of complement is involved in the pathogenesis of arthritis much issues are not well elucidated. The aim of the present study was to evaluate...

Verbascum xanthophoeniceum Griseb. is an endemic plant of the Balkan region, a representative of the genus Verbascum used in traditional medicine for respiratory and inflammatory disorders. The objective of this study was to evaluate in vivo and in vitro the antiinflammatory action of crude extract, different fractions and pure compounds obtained f...

Introduction Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). Methods Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and wild-type (WT) C57BL/6 mice. Sy...

FcγR expression on synovial and blood neutrophils and on monocytes in properdin-deficient mice with CAIA. (A) FcγR was expressed on blood wild-type Ly6G+ cells but not on properdin-deficient cells, as shown in one individual experiment. Frequencies of Ly6G+ FcγR+ in blood at day 10 of disease are presented on the graph. Data are expressed as the me...

This study was designed to examine the potential ability of Candida albicans DNA to influence joint inflammation in a mouse model of zymosan-induced arthritis (ZIA) relating to Toll-like receptor-9 (TLR9) expression and cytokine production in different compartments. To induce ZIA, mice were injected in the ankle joint with 180 μg zymosan. TLR9 expr...

In infectious diseases polymorphonuclear neutrophils produce diverse cytokines, amongst which are IL-4 and IFN-γ. In order to consider the ability of neutrophils to synthesize these molecules with opposing actions in arthritic conditions, BALB/c and SCID mice were injected intra-articularly with zymosan. Our research showed that arthritis was less...

Synthesis, absorption and fluorescence properties of a series of asymmetrical monomethine cyanine dyes, chloro-containing analogs of Thiazole orange, are reported. Their staining ability was studied by flow cytometry. The saturating concentrations of each dye that gives a stable staining intensity have been determined. The ability of dyes B9, B11,...

Figure S2. Effect of glucosamine on osteoclast differentiation in vitro. Bone marrow cells from healthy mice were isolated, resuspended at 1 × 106/ml in MEM medium (Lonza, Verviers, Belgium) containing 10% FCS and 50 ng/ml of macrophage colony-stimulating factor and cultured for one day. Osteoclasts were generated after six days of culture with 100...

Figure S1. Administration of glucosamine in severe CIOA. ICR mice were injected with high dose of collagenase (two i.a. injections with 2 U/mouse at Day 0 and Day 2). After 7 days glucosamine hydrochloride was administered orally at a dose of 20 mg/kg for 20 days. (a) Representative joint sections stained with H&E showed a mild effect of glucosamin...

Cell suspension and Agrobacterium rhizogenes-transformed hairy root cultures of Devil’s claw (Harpagophytum procumbens), an African plant with high medicinal value, were cultivated in shake-flasks. A purification scheme to isolate their main active constituents (the phenylethanoid glycosides verbascoside, leucosceptoside A, β-OH-verbascoside and ma...

Glucosamine is an amino-monosaccharide and precursor of glycosaminoglycans, major components of joint cartilage. Glucosamine has been clinically introduced for the treatment of osteoarthritis but the data about its protective role in disease are insufficient. The goal of this study was to investigate the effect of long term administration of glucos...

Joint destruction and excessive bone formation are associated with high expression of soluble receptor activator of nuclear factor-κB ligand (sRANKL). This study was undertaken to investigate the role of sRANKL in collagenase-induced osteoarthritis (CIOA) in mice and in patients with osteoarthritis (OA). The initial phase of CIOA was associated wit...

Cell suspension and Agrobacterium rhizogenes-transformed hairy root cultures of Devil’s claw (Harpagophytum procumbens), an African plant with high medicinal value, were cultivated in shake-flasks. A purification scheme to isolate their main active constituents (the phenylethanoid glycosides verbascoside, leucosceptoside A, b-OH-verbascoside and ma...

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with unknown etiology which results in the destruction of cartilage and bone. All main immunological components play a fundamental role in the initiation, dissemination and perpetuation of autoimmune process in RA. The precise control of cellular and immunological events leading t...

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with the destruction of cartilage and bone. Experimental models of RA perform a great platform to study the mechanisms involved in the pathogenesis of the disease. In the present review, most popular animal models of RA are described. Data on experimental models induced by injec...

Using properdin-deficient and wild-type mice, we have investigated the role of properdin in development and progression of zymosan-induced arthritis. At the initial phase of local, zymosan-induced inflammation, properdin-deficient and wild-type mice showed bone erosion, proteoglycan loss and cell infiltration. Compared to wild-type, properdin-defic...

Joint destruction and excessive bone loss in osteoarthrosis (OA) and rheumatoid arthritis are associated with changes in expression of some cell receptors and molecules as well as in sera levels of some cytokines. Aim of the study was to examine the level of soluble receptor activator of nuclear factor KB ligand (sRANKL) in sera and its expression...

Zymosan-induced shock has been associated with an increased production of pro-inflammatory cytokines and mediators, causing a generalized dysfunction of liver, lung and kidneys. Herein, we investigate the effects of tyrphostin AG-490 on the early inflammation and on the late renal injury provoked by zymosan injection. Shock was induced by intraperi...

Two isochinoline alkaloids, glaucine and oxoglaucine were investigated for their suggested anti-inflammatory influence concerning nitric oxide and cytokine production. Mouse peritoneal macrophages were stimulated with different Toll-like receptor (TLR) ligands such as LPS for TLR4, zymosan for TLR2 and CpG for TLR9. The alkaloids inhibited TNF-alph...

Neonates are highly sensitive to infections because they are biased to develop Th2 immune responses. When exposed to certain agents, such as DNA vaccines or CpG DNA motifs, neonates are capable to mount adult-like Th1 protective responses. This study investigates the capacity of Candida albicans (C. albicans) dsDNA to induce host resistance in newb...

In the present study, we have investigated comparatively the inflammatory response of patients with active and inactive osteoarthritis. The sera from 31 healthy individuals, 37 patients with active OA, and 19 patients with inactive OA were assayed for TNF-alpha, IL-6, sRANKL, RANTES, and MRP8 using ELISA in order to evaluate their potential as mark...

Tyrphostins, derivatives of benzylidene malononitrile are recognized as tyrosine kinase inhibitors that have been applied in some models of acute inflammatory conditions, like LPS and zymosan-induced shock. In the present study, we have investigated the effects of tyrphostin AG-490, on the development of multiple organ failure induced by i.p. injec...

In this study, double-stranded Candida albicans DNA was administered in systemic C. albicans infection in at dose of 20 microg per mouse at 4, 5 and 6 weeks of age. The level of IL-12 in serum was elevated as a result of yeast DNA treatment and correlated with lower mortality and decreased kidney and liver injury. Macrophage activation was demonstr...

Extracellular enzymes secreted by Candida albicans are claimed to be virulence factors responsible for penetration of the yeast into host cells. Substances able to inhibit lipolytic and proteinase activities of the fungus might be of therapeutic use in some pathologic conditions caused by C. albicans. In the present work, we have tested the influen...

Hereditary properdin deficiency is linked to susceptibility to meningococcal disease (Neisseria meningitidis serotypes Y and W-135) with high mortality. Its relative contribution toward the outcome of nonseptic shock has not been investigated. Using properdin-deficient C57BL/6 mice and their littermates, this study examines their survival of zymosa...

Zymosan-induced generalized inflammation is a convenient model to study the process of acute and chronic inflammatory processes resulting in multiple organ dysfunction syndrome. Macrophages as a source of many pro-inflammatory mediators are the major players in shock and further organ failure. Etoposide is a cytostatic drug known to reduce macropha...

In the present research, the inflammatory response was compared in patients with activated and non-activated osteoarthritis. There were investigated 37 patients with activated osteoarthhtis, 19 with non-activated osteoarthritis and 31 healthy controls. By the use of ELISA method, the following inflammatory markers were tracked - TNF-α, IL-6, sRANKL...

Vasoactive intestinal peptide (VIP) was administered in a model of zymosan-induced generalized inflammation (ZIGI). Its beneficial action was associated with reduced TNF-alpha and increased IL-10 production, lowered levels of creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin in circulation. VIP diminished th...

Recently, a relationship between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the beta-amyloid precursor protein (betaAPP) in relationship with the pathogenesis of Alzheimer's disease (AD) has been suggested. Therefore, we studied the specific activity of GAPDH in the different animal models of AD: transgenic mice (Tg2576) and rats treated...