Adipokine receptor expression in mast cells is altered by specific ligands and proinflammatory cytokines.

Adipokines play essential roles in regulating a range of biological processes, but growing evidence indicates that they are also fundamental in immunological mechanisms and, primarily, inflammatory responses. Adipokines mediate their actions through specific receptors. However, although adipokine receptors are widely distributed in many cell and tissue types, limited data are available on their expression in mast cells (MCs) and, consequently, adipokine's significance in the modulation of MC activity within the tissues. In this study, we demonstrate that rat peritoneal MCs constitutively express the leptin receptor (i.e. LEPR), adiponectin receptors (i.e. ADIPOR1 and ADIPOR2) and the chemerin receptor (i.e. CMKLR1). We also found that LEPR, ADIPOR1, ADIPOR2 and CMKLR1 expression in MCs changes in response to stimulation by their specific ligands and some cytokines with potent proinflammatory properties. Furthermore, the involvement of intracellular signaling molecules in leptin-, adiponectin- and chemerin-induced MC response was analyzed. Overall, our findings suggest that adipokines leptin, adiponectin and chemerin can significantly affect the activity of MCs in various processes, especially during inflammation. These observations may contribute significantly to understanding the relationship between adipokines, immune mechanisms and diseases or conditions with an inflammatory component.

Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy. AIMS: The study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women's neonates and fetuses born to mothers with GDM. MATERIALS AND METHODS: Cord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit. RESULTS: Fetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age. CONCLUSION: These findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

The Microbiota-Gut-Brain Axis in Psychiatric Disorders.

Modulating the gut microbiome and its influence on human health is the subject of intense research. The gut microbiota could be associated not only with gastroenterological diseases but also with psychiatric disorders. The importance of factors such as stress, mode of delivery, the role of probiotics, circadian clock system, diet, and occupational and environmental exposure in the relationship between the gut microbiota and brain function through bidirectional communication, described as "the microbiome-gut-brain axis", is especially underlined. In this review, we discuss the link between the intestinal microbiome and the brain and host response involving different pathways between the intestinal microbiota and the nervous system (e.g., neurotransmitters, endocrine system, immunological mechanisms, or bacterial metabolites). We review the microbiota alterations and their results in the development of psychiatric disorders, including major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD).

The impact of TLR7 agonist R848 treatment on mast cell phenotype and activity.

Bearing in mind that mast cell contribution to viral clearance is still not fully understood, in this study, we evaluated the effect of Toll-like receptor (TLR)7 viral single-stranded ribonucleic acid (ssRNA) mimic ligand, namely resiquimod (R)848, on mast cell phenotype and activity. We demonstrated that rat peritoneal mast cells exhibit surface and intracellular expression of ssRNA-specific TLR7 molecule, and that mimic ligand switches the self-expression of this receptor. We also detected other proteins associated with the cellular antiviral response: interferon-alpha receptor 1 (IFNAR1), interferon-gamma receptor 1 (IFNGR1), and major histocompatibility complex I (MHC I). Moreover, we showed that R848 caused the decrease of all molecule's expression after prolonged incubation. Interestingly, we found that R848 induced the increase of high-affinity IgE receptor (FcεRI) expression. Finally, we documented that TLR7 ligand-stimulated mast cells synthesize/release interferon (IFN)-α and -ß, tumor necrosis factor (TNF), and chemokines CCL3, CXCL8, as well as pro-inflammatory lipid mediators. Our findings confirm that mast cells may respond to TLR7 ligand by altering their phenotype and synthesizing mediators and could serve as active participants in the antiviral immune response.

Mast cell phenotypic plasticity and their activity under the influence of cathelicidin-related antimicrobial peptide (CRAMP) and IL-33 alarmins.

Invading pathogens are contained/eliminated by orchestrated actions of different humoral components of the innate immune response. One of them is endogenous molecules called alarmins, which contribute to diverse processes from danger sense until the infection extinction. Considering the participation of mast cells (MCs) in many aspects of the body's defense and, on the other hand, the importance of alarmins as molecules that signal damage/danger, in this study, we evaluated the effect of alarmins on MC phenotype and activity. We found that cathelicidin CRAMP and cytokine IL-33 significantly affect the appearance of Dectin-1, Dectin-2, RIG-I, and NOD1 receptors in mature MCs and modulate their inflammatory response. We established that chosen alarmins might stimulate MCs to release pro-inflammatory and immunoregulatory mediators and induce a migratory response. In conclusion, our data highlight that alarmins CRAMP and IL-33 might strongly influence MC features and activity, mainly by strengthening their role in the inflammatory mechanisms and controlling the activity of cells participating in antimicrobial processes.

Analysis of IL-1ß, CXCL8, and TNF-α levels in the crevicular fluid of patients with periodontitis or healthy implants.

BACKGROUND: Our study aimed to assess the level of IL-1ß, CXCL8, and TNF-α in peri-implant sulcular fluid (PISF) collected from patients with no clinical symptoms of mucositis or peri-implantitis and compare them with cytokine concentration in gingival crevicular fluid (GCF) acquired from patients with healthy periodontium and those with varying severity of periodontitis. METHODS: A total of 189 subjects were included in the study, and GCF/PISF samples were checked for IL-1ß, CXCL8, and TNF-α levels using an ELISA test. RESULTS: The IL-1ß level in PISF in patients with implants was significantly lower than in GCF in patients with mild, moderate, or severe periodontitis. The CXCL8 level in PISF was considerably lower than in patients with moderate periodontitis. The TNF-α level in PISF in patients with implants was markedly higher compared to subjects with healthy periodontium or patients with mild periodontitis. CONCLUSION: Analysis of cytokine levels may help describe the pathogenesis and early diagnosis of peri-implantitis and prevision in high-risk patients.

Adipocytokines leptin and adiponectin function as mast cell activity modulators.

A growing body of data indicates that adipocytokines, including leptin and adiponectin, are critical components not only of metabolic regulation but also of the immune system, mainly by influencing the activity of cells participating in immunological and inflammatory processes. As mast cells (MCs) are the key players in the course of those mechanisms, this study aimed to evaluate the impact of leptin and adiponectin on some aspects of MC activity. We documented that in vivo differentiated mature tissue MCs from the rat peritoneal cavity express a receptor for leptin (OB-R), as well as receptors for adiponectin (AdipoR1 and AdipoR2). We established that leptin, but not adiponectin, stimulates MCs to release of histamine as well as to generation of cysteinyl leukotrienes (cysLTs) and chemokine CCL2. We also found that both adipocytokines affect mRNA expression of various cytokines/chemokines. Leptin and adiponectin also activate MCs to produce reactive oxygen species. Moreover, we documented that leptin significantly augments the surface expression of receptors for cysLTs, i.e. CYSLTR1, CYSLTR2, and GPR17 on MCs, while adiponectin increases only GPR17 expression, and decreases CYSLTR2. Finally, we showed that both adipocytokines serve as potent chemoattractants for MCs. In intracellular signaling in MCs activated by leptin Janus-activated kinase 2, phospholipase C, phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK1/2), and p38 molecules play a part whereas the adiponectin-induced activity of MCs is mediated through PI3K, p38, and ERK1/2 pathways. Our observations that leptin and adiponectin regulate MC activity might indicate that adipocytokines modulate the different processes in which MCs are involved.

Expression of Toll-like receptors 2 and 4 on peripheral mononuclear cells (PBMCs) after laparoscopic cholecystectomy.

Increasing evidence suggests that the course and intensity of inflammation, as well as repair processes, developed in response to stress, injury, and trauma, depend on the interaction between immediately released endogenous molecules, called alarmins or danger/damage-associated molecular patterns (DAMPs) and cellular pattern recognition receptors (PRR) including Toll-like receptors (TLRs) and activation of inflammatory/immune cells. Therefore, the aim of this study was to examine the expression of TLRs in peripheral blood mononuclear cells (PBMCs), CD3+, and CD14+ cells in control group and in patients before the laparoscopic cholecystectomy, and three and seven days after surgery. Flow cytometry was used to evaluate expression of TLR2 and TLR4. TLR2 and especially TLR4 expression levels on PBMCs were significantly lower in patients with asymptomatic cholelithiasis than in the control group. Laparoscopic surgery did not induce the significant changes in the expression of TLR2, both on PBMCs and CD3+ and CD14+ cell subpopulations. On the contrary, TLR4 expression level on PBMCs was significantly lower on the third and seventh postoperative day than before surgery. Collectively, the expression levels of cellular TLRs, and especially TLR2 and TLR4, might strongly influence the responsiveness of cells to DAMP activation, and in this way can regulate the intensity of inflammatory response to surgical injury.

Body composition does not affect serum levels of cathelicidin LL-37 in elderly women with unipolar depression.

OBJECTIVES: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in elderly women with depression. The aim of this study is to evaluate serum LL-37 levels in elderly women with depression and to compare them with non-depressed elderly women, matched for anthropometric and body composition parameters. METHODS: Forty women with unipolar depression and 23 non-depressed women (age ≥60 years) were included into the study. Anthropometric measurements and biochemical analyzes were performed. Concentration of LL-37 in serum was assessed using ELISA method. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). RESULTS: There was a statistically significant difference (p =.038) in serum LL-37 level between patients with depression (3.55 ± 6.57 ng/mL) and control subjects (2.01 ± 3.88 ng/mL). Apart from visceral adipose tissue mass (%) in the depression group, we found no associations between serum LL-37 and analyzed anthropometric or body composition parameters. CONCLUSIONS: Results of this study indicate that with the exception of visceral adipose tissue, LL-37 serum levels are not affected by anthropometric or body composition parameters. The association between visceral adipose tissue and LL-37 may indicate that visceral fat could be responsible for the increased LL-37 production.

Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections.

Nowadays, data indicate that antimicrobial peptides play an important role in immunological defense. Human cathelicidin LL-37 possesses a broad spectrum of antimicrobial properties against Gram-positive and Gram-negative bacteria, and is thereby an important component of defense mechanisms within the respiratory tract. In this study, we determined the LL-37 serum level in patients with pneumonia caused by different bacteria species in comparison with healthy subjects. Twenty-two patients with pneumonia caused by coccal Gram-positive bacteria (I), 16 patients with pneumonia caused by Haemophilus influenzae (II), 29 patients with pneumonia caused by members of the Enterobacteriaceae (III), 13 patients caused by non-fermenting Gram-negative bacteria (IV), and 30 healthy controls were enrolled in the study. Serum LL-37 concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The mean LL-37 concentration in pneumonia patients was significantly higher in group I (p = 0.0032), group II (p = 0.0022), and group III (p = 0.019), and significantly lower in group IV (p = 0.000004) as compared with healthy volunteers. Our data suggest that LL-37 plays an important role in defense mechanisms during pneumonia. The reduced level of this peptide in subjects with pneumonia caused by opportunistic bacteria may reflect weakened immune system reactivity in these patients.

[Alternatives for antibiotics - antimicrobial peptides and phages].

The constant increase in the number of bacteria resistant to antibiotics poses a substantial problem for the therapy of infectious diseases of different etiologies. The growing insensitivity of pathogens on the classical methods of treatment is associated mainly with multiple mechanisms of resistance created by bacteria. Furthermore, no proper antibiotic treatment causes the appearance of resistant strains even at the last line drugs. Therefore, there are still being sought alternatives in the treatment of difficult to eradicate pathogens. The antimicrobial peptides including cathelicidins, defensins, lysozyme, lactoferrin, histatins and bacteriocins arouse huge interest as potential therapeutics. They exhibit a broad spectrum of activity against many Gram-positive and Gram-negative bacteria, but also against fungi. Moreover, they are considered much safer than antibiotics, due to the fact that they are present in all eukaryotic organisms, in which they are an essential element of the immune system. In addition, phage therapy is also strongly recommended as alternative antibacterial approach. In this review we highlight the potential uses of antimicrobial peptides and bacteriophages in the treatment of infections of various etiologies.

Expression of surface and intracellular Toll-like receptors by mature mast cells.

Nowadays, more and more data indicate that mast cells play an important role in host defense against pathogens. That is why it is essential to understand the expression of Toll-like receptors (TLRs) by mast cells, because these molecules play particularly significant role in initiation host defense against microorganisms as they recognize both wide range of microbial pathogen-associated molecular patterns (PAMPs) and various endogenous damage-associated molecular patterns (DAMPs) released in response to infection. Therefore, we examined the constitutive expression of both surface and endosomal TLRs in rat native fully mature tissue mast cells. By the use of qRT-PCR we found that these cells express mRNAs for TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9. The expression of TLR3, TLR4, TLR5, TLR7, and TLR9 transcripts were low and comparable and only the expression of TLR2 transcript was significant. By the use of flow cytometry technique, we clearly documented that mast cells express TLR2, TLR4, and TLR5 on cell surface, while TLR3, TLR7, and TLR9 proteins are located both on the cell membrane and intracellularly. The highest expression was observed for TLR5 and the lowest for surface TLR7. These observations undoubtedly indicate that mature tissue mast cells have a broad set of TLR molecules, thus can recognize and bind bacterial, viral, and fungal PAMPs as well as various endogenous molecules generated in response to infection.

Antioxidant and Anti-Inflammatory Effects of Carotenoids in Mood Disorders: An Overview.

Depression has a multifactorial etiology comprising family history and unemployment. This review aims to summarize the evidence available for the antioxidant and anti-inflammatory effects of carotenoids in mood disorders. This review article's methodologies were based on a search of the PubMed database for all linked published papers. Epidemiological studies indicate that a diet rich in vegetables, fruits, nuts, fish, and olive oil may prevent the development of depression. Antioxidant supplementation has been found to combat various stress-induced psychiatric disorders, including depression and anxiety. A growing body of evidence indicates that carotenoids have both antioxidant and anti-inflammatory. Studies also suggest that poor dietary intake, particularly low intakes of fruit and vegetables and high intakes of fast food and other convenience foods, may increase the risk of developing depression. Thus, dietary interventions have the potential to help mitigate the risk of mental health decline in both the general population and those with mood disorders. Considering that carotenoids have both antioxidant and anti-inflammatory effects, it is expected that they might exert a promising antidepressant effect. Nevertheless, further studies (including interventional and mechanistic studies) assessing the effect of carotenoids on preventing and alleviating depression symptoms are needed.

Assessment of knowledge among patients of surgical wards regarding clinical symptoms and diagnostics of the most common malignant tumors.

AIM OF THE STUDY: The aim of this work was to evaluate the knowledge of symptoms and prophylaxis among hospitalized patients. MATERIAL AND METHODS: The research was carried in the Provincial Hospital in Bydgoszcz (i.e. general surgery, gynecology and obstetrics, urology, breast surgery and thoracic surgery). 250 hospitalized patients took part in the tests, as well as 50 healthy people. The scientific method used was a specially designed questionnaire. The Bioethics Committee of Collegium Medicum of Mikolaj Kopernik University in Bydgoszcz approved these tests. RESULTS: Patients from the Breast Diseases Ward had better knowledge about cancers than the control group. Symptoms of lung cancer were known to both groups to the same extent. Patients from the Clinical Ward of Thoracic Surgery were very knowledgeable about lung cancer, but they did not know anything about other malignant types of cancer. Patients from Gynecology and Obstetrics wards are better than the control group only at knowledge about symptoms and screening of cervix cancer. Patients from the Urology Ward have the best knowledge about screening of prostate cancer and colon cancer. Those hospitalized at the Surgery Ward do not know symptoms of colon cancer, but they have knowledge about its screening. CONCLUSIONS: Patients from the Clinical Ward of Thoracic and Cancer Surgery and the Clinical Surgery Ward had the least knowledge about malignant tumors.Patients from Urology, Gynecology and Obstetrics wards have better knowledge about malignant tumors treated there.

Different effectiveness of fungal pathogen-associated molecular patterns (PAMPs) in activating rat peritoneal mast cells.

Mast cells (MCs) are the first immune cell type that can contact with the external environment, where they may rapidly sense the presence of pathogens. These cells are directly involved in innate defense through their ability to pathogen destruction by several mechanisms and the pattern recognition receptors (PRRs) they express. Several studies have focused on the aspects of MC responses to bacterial and viral pathogens or their specific components and the role of those cells in antibacterial or antiviral defense mechanisms. However, to date, the knowledge of the influence of various fungi-derived molecules on MC activity is primarily based on limited data. Thus, this study aims to compare the effect of the major fungi cell wall-associated antigens, i.e., two ß-(1,3)-glucans: zymosan - ß-(1,3)-glucan containing mannan and chitin, and curdlan - purified linear model ß-(1,3)-glucan as well as mannan on peritoneal MC activity. In particular, the potency of various fungal cell wall components to induce MC migration, degranulation, and generation and/or release of de novo-synthesized mediators/cytokines/chemokines was analyzed. The most striking result to emerge from the data is that MC activation differs depending on the fungal stimuli. Our study outlines that components of the inner layer of the fungi cell wall - ß-glucans, i.e., zymosan and curdlan, are more potent stimulators of MC activity compared to mannan. On this note, the data described here may provide a foundation for further studying the role of MC in antifungal immunity and be helpful for a better understanding of host-pathogenic fungi interactions.

Serum Levels and in vitro CX3CL1 (Fractalkine), CXCL8, and IL-10 Synthesis in Phytohemaglutinin-Stimulated and Non-stimulated Peripheral Blood Mononuclear Cells in Subjects With Schizophrenia.

Introduction: Although schizophrenia is a severe mental illness, whose etiology is still largely unknown, its pathogenesis may be associated with dysregulation of the immune mechanisms. The present study compares the levels of interleukin (IL)-10, interleukin-8 (CXCL8), and fractalkine (CX3CL1) between schizophrenia patients and healthy controls. It also assesses the ability of peripheral peripheral blood mononuclear cells (PBMCs) to produce these cytokines spontaneously and following mitogen-stimulation. Materials and Methods: A prospective study was performed of 60 adult schizophrenia patients and 32 controls. CXCL8, IL-10, and fractalkine concentrations were measured in serum and supernatants from cultured PBMCs. Anthropometric (BMI, WHR) and body composition measurements were taken using bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Results and Conclusion: The schizophrenia patients demonstrated significantly higher levels of serum CXCL8 (schizophrenia: 13.4 ± 15.7 pg/mL, control: 6.9 ± 4.2 pg/mL, p = 0.001) and lower level of serum fractalkine (schizophrenia: 22.8 ± 9.9 pg/mL, control: 45.4 ± 84.5 pg/mL, p = 0.041). Serum IL-10 levels did not significantly differ. No in vitro synthesis of fractalkine was observed. Neither unstimulated or PHA-stimulated CXCL8 secretion differed between the two groups (p >0.05). The patients not taking mood stabilizers (MS-) demonstrated significantly higher CXCL8 levels than those on mood stabilizers (MS+) (p = 0.03) and control (p < 0.001). In addition, the MS- sub-group demonstrated significantly lower serum fraktalkine than controls (p = 0.009). These effects could be described as pseudo-normalization of CXCL8 and fractalkine in schizophrenia patients taking mood stabilizers.

Hypoxia modulates human mast cell adhesion to hyaluronic acid.

Hypoxia is an inherent factor in the inflammatory process and is important in the regulation of some immune cell functions, including the expression of mast cell pro- and anti-inflammatory mediators. Hypoxia also influences cell adhesion to the extracellular matrix (ECM). Hyaluronic acid is one of the major components of the ECM that is involved in inflammatory and tissue regeneration processes in which mast cells play a prominent role. This prompted us to investigate the effects of hypoxia on the expression of hyaluronic acid receptors in mast cells and mast cell adhesion to this ECM component. We found that human LAD2 mast cells spontaneously adhered to hyaluronic acid in a CD44-dependent manner and that reduced oxygen concentrations inhibited or even completely abolished this adhesion process. The mechanism of hypoxia downregulation of mast cell adhesion to hyaluronic acid did not involve a decrease in CD44 expression and hyaluronidase-mediated degradation of adhesion substrates but rather conformational changes in the avidity of CD44 to hyaluronic acid. Hypoxia-mediated regulation of mast cell adhesion to extracellular matrix components might be involved in the pathogenic accumulation of mast cells observed in the course of certain diseases including rheumatoid arthritis and cancer.

Systemic concentration of apelin, but not resistin or chemerin, is altered in patients with schizophrenia.

It has been suggested that immune-inflammatory processes might be involved in the etiopathogenesis of schizophrenia. Since growing evidence indicates that adipokines strongly modulate the course of immune response and inflammatory processes, it is currently suggested the contribution of those factors in the etiology of schizophrenia as well. The aim of this study was to determine the serum levels of 4 adipokines-apelin, resistin, chemerin, and omentin-in patients with schizophrenia as compared with healthy subjects. Fifty-seven adult patients with schizophrenia and 31 healthy volunteers were included in this prospective study. ELISA was used to measure the serum concentration of resistin, apelin, omentin-1, and chemerin. No difference in the mean concentration of resistin (p=0.20) and chemerin (p=0.30) between patients with schizophrenia and the healthy group was observed. Apelin concentration was significantly (p=0.004) lower in patients with schizophrenia as compared with controls. A significant difference in apelin level between men with schizophrenia and control group (p=0.04) was reported. Apelin concentration was significantly correlated with waist-to-hip ratio, whereas chemerin concentration was significantly correlated with the Positive and Negative Syndrome Scale G score. There exists evidence that apelin might be involved in the pathogenesis of schizophrenia.

Alarmins (IL-33, sST2, HMGB1, and S100B) as potential biomarkers for schizophrenia.

There is growing evidence that immune/inflammatory processes are related to the etiology of schizophrenia. Danger-/damage-associated molecular patterns (DAMPs), also called alarmins, are recognized as inflammatory mediators that play an important role in the development of many infection-induced or sterile inflammatory diseases. The importance of DAMPs particles in various mental disorders is still not clear. Therefore, this study aimed to evaluate serum levels of the most promising alarmins (IL-33, sST2, HMGB1, and S100B), as potent schizophrenia biomarkers. Sixty-eight adult patients with chronic schizophrenia and twenty-nine healthy volunteers were included in this prospective study. Enzyme-linked immunosorbent assay (ELISA) was used to assess the serum concentration of IL-33, sST2, HMGB1, and S100B. We documented that the serum levels of IL-33 (p = 0.006), sST2 (p = 0.02), HMGB1 (p = 0.01), and S100B (p = 0.04) are significantly higher in patients with schizophrenia than in healthy subjects. In male, but not in female, patients with schizophrenia, we found a significant difference in the serum IL-33, sST2, and HMGB1 concentrations as compared to the healthy men. In both male and female patients with schizophrenia, there was no significant difference in the serum concentrations of S100B in comparison to control subjects. In patients with schizophrenia, no significant correlations were noticed neither between any studied alarmins and PANSS scores nor between CDSS scores. Given that all investigated alarmins participate in the course of the neuroinflammatory process, they might be considered as biomarkers of neuroinflammatory process underlying schizophrenia. Based on our observations, it seems that the most useful biological indicator of schizophrenia would be IL-33.

Native and IgE-primed rat peritoneal mast cells exert pro-inflammatory activity and migrate in response to yeast zymosan upon Dectin-1 engagement.

Mast cells (MCs) play an essential role in host defense, primarily because of their location, their ability to pathogen destruction via several mechanisms, and the pattern recognition receptors they express. Even though most data is available regarding MC activation by various bacteria- or virus-derived molecules, those cells' activity in response to constituents associated with fungi is not recognized enough. Our research aimed to address whether Saccharomyces cerevisiae-derived zymosan, i.e., ß-(1,3)-glucan containing mannan particles, impacts MC activity aspects. Overall, the obtained results indicate that zymosan has the potential to elicit a pro-inflammatory response of rat peritoneal MCs. For the first time ever, we provided evidence that zymosan induces fully mature MC migration, even in the absence of extracellular matrix (ECM) proteins. Moreover, the zymosan-induced migratory response of MCs is almost entirely a result of directional migration, i.e., chemotaxis. We found that zymosan stimulates MCs to degranulate and generate lipid mediators (cysLTs), cytokines (IFN-α, IFN-ß, IFN-γ, GM-CSF, TNF), and chemokine (CCL2). Zymosan also upregulated mRNA transcripts for several cytokines/chemokines with pro-inflammatory/immunoregulatory activity. Moreover, we documented that zymosan activates MCs to produce reactive oxygen species (ROS). Lastly, we established that the zymosan-induced MC response is mediated through activation of the Dectin-1 receptor. In general, our results strongly support the notion that MCs contribute to innate antifungal immunity and bring us closer to elucidate their role in host-pathogenic fungi interactions. Besides, provided findings on IgE-sensitized MCs appear to indicate that exposure to fungal zymosan could affect the severity of IgE-dependent disorders, including allergic ones.