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.

Suggested mechanism of CCR5Δ32, CCR2-64I and SDF 1-3'A allele frequency change in Polish and Lithuanian gene pools from the perspective of passing time.

The study aimed to determine the frequency of the alleles associated with hereditary immune response in 16 historical populations and assess which evolutionary forces may have contributed to the observed frequency fluctuation. The analysed polymorphic sites are located in three genes - CCR5, CCR2 and SDF 1 (CXCL12). Protein products are involved in the innate immune response and are also involved in various types of infections, autoimmune diseases and tumours. The frequency of the alleles found in the DNA of the studied individuals was determined by the Sanger methodology and was compared with the data obtained for modern populations. To confirm the authenticity of the obtained results, mtDNA HVRI haplotypes of all the studied samples were obtained and compared with the genetic database of the laboratory personnel who came into contact with the studied material. Based on the variability of allele frequency, advanced biostatistical analysis was used to distinguish the effect of natural selection from genetic drift, i.e. the forces operating on the polymorphic sites studied. All procedures were performed according to the guidelines for working with ancient DNA to avoid contamination with modern DNA molecules. 681 samples from 39 archaeological sites in Poland and Lithuania dated to the 40th century BC and the 19th century were studied. The biostatistical analysis showed that the fluctuations in the frequency of CCR5Δ32 in the analysed time interval could be mainly the effect of genetic drift. Nevertheless, for CCR2-64I and SDF 1-3'A, the results confirm the suggestion of negative selection as the mechanism involved. Since all the polymorphic sites encode the elements of innate immune response that are indirectly associated with the process of an HPV infection and the development of cervical cancer, the human papillomavirus may be a good candidate for a selection coefficient affecting the frequency of CCR2-64I and SDF 1-3'A. However, for CCR5Δ32, selection was not detected despite its proven role in the molecular mechanism involved in the response to an HPV infection. The presented work seems to be the first in which the problem of the pattern of CCR5Δ32, CCR2-64I and SDF 1-3'A frequency fluctuations in a temporal perspective was discussed, proposing HPV as a factor influencing the occurrence of the CCR2 and SDF1 alleles.

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.

Do Mast Cells Contribute to the Antifungal Host Defense?

The fungal kingdom includes a group of microorganisms that are widely distributed in the environment, and therefore the exposure to them is almost constant. Furthermore, fungal components of the microbiome, i.e., mycobiome, could serve as a reservoir of potentially opportunistic pathogens. Despite close encounters with fungi, defense mechanisms that develop during fungal infections remain unexplored. The strategic location of mast cells (MCs) close to the external environment places them among the first cells to encounter pathogens along with the other innate immune cells. MCs are directly involved in the host defense through the ability to destroy pathogens or indirectly by activating other immune cells. Most available data present MCs' involvement in antibacterial, antiviral, or antiparasitic defense mechanisms. However, less is known about their contribution in defense mechanisms against fungi. MCs may support immune responses to fungi or their specific molecules through initiated degranulation, synthesis and release of cytokines, chemokines, mediators, and generation of reactive oxygen species (ROS), as well as immune cells' recruitment, phagocytosis, or provision of extracellular DNA traps. This review summarizes current knowledge on host defense mechanisms against fungi and MCs' involvement in those processes. It also describes the effects of fungi or fungus-derived constituents on MCs' activity.

Evaluation of circulating CD34+ stem cells in peripheral venous blood in patients with varying degrees of periodontal disease.

INTRODUCTION: Periodontal disease presents a challenge for modern medicine, and research on the use of stem cells as a treatment is currently underway. MATERIAL AND METHODS: The study included 45 patients who were given a thorough physical examination. Additionally, an evaluation of their medical history of the disease, degree of progression of periodontal disease, and the level of CRP in the blood was carried out. Patients were divided into 4 groups: 4 patients were in the first group with no periodontal disease, 8 patients in the second group with a moderate level, 20 patients in the third group with an advanced level, and 13 patients in the fourth group were toothless. For each group, the use of stem cells as a treatment of antibody-labeled CD34+ stem cells, lymphocytes, and leukocytes was conducted. RESULTS: A statistically significant positive correlation was observed in CD34+ stem cells in proportion to lymphocytes in the moderate (0.80), in the advanced (0.75), and in the toothless groups (0.70). The ratio of CD34+ stem cells to leukocytes was statistically significant in the toothless group (0.92) and in the advanced group (0.91). A statistically significant increase was noted in the level of CRP in the previously mentioned groups of patients, and the highest concentration of CD34+ stem cells in the advanced group. CONCLUSIONS: The highest concentration of CD34+ cells was observed in the group of patients with advanced periodontal disease.

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.

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.

Expression of Dopamine D1-4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D1, D2, D3, D4 and serotonin 5-HT1A, 5-HT2A, and 5-HT3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects. Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D1-4 and serotonin 5-HT1A-3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC50, half of IC50, and one-quarter of IC50 concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D1, D2 and D4 receptors (p < 0.001), and significantly lower mRNA expression of 5-HT3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D1 lost its significance, while that of D3, 5-HT1A, 5-HT2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors. Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.

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.

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.

Mannan activates tissue native and IgE-sensitized mast cells to proinflammatory response and chemotaxis in TLR4-dependent manner.

Mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, exert several essential mechanisms of pathogen destruction, and they express pattern recognition receptors. Accumulating evidence indicates that these cells are involved in the control and clearance of bacterial, viral, or parasitic infections, but much less is known about their contribution in defense against fungi. The study was aimed to establish whether mannan, which comprises an outermost layer and major structural constituent of the fungal cell wall, may directly stimulate tissue mast cells to the antifungal response. Our findings indicate that mannan activates mast cells isolated from the rat peritoneal cavity to initiate the proinflammatory response. We found that mannan stimulates mast cells to release histamine and to generate cysteinyl leukotrienes, cytokines (IFN-γ, GM-CSF, TNF), and chemokines (CCL2, CCL3). It also increased the mRNA expression of various cytokines/chemokines. We also documented that mannan strongly activates mast cells to generate reactive oxygen species and serves as a potent chemoattractant for these cells. Furthermore, we established that mannan-induced activity of mast cells is mediated via TLR4 with the involvement of the spleen tyrosine kinase molecule. Taking together, our results clearly support the idea that mast cells act as sentinel cells and crucially determine the course of the immune response during fungal infection. Additionally, presented data on IgE-coated mast cells suggest that exposure to fungal mannan could influence the severity of IgE-dependent diseases, including allergic ones.

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.

Archaea Occurrence in the Subgingival Biofilm in Patients with Peri-implantitis and Periodontitis.

This study aimed to determine the prevalence and diversity of archaea and select bacteria in the subgingival biofilm of patients with peri-implantitis in comparison to patients with unaffected implants and patients with periodontitis. Samples of subgingival biofilm from oral sites were collected for DNA extraction (n = 139). A 16S rRNA gene-based polymerase chain reaction assay was used to determine the presence of archaea and select bacteria. Seven samples were selected for direct sequencing. Archaea were detected in 10% of samples from peri-implantitis sites, but not in samples from the unaffected dental implant. Archaea were present in 53% and 64% of samples from mild and moderate/advanced periodontitis sites, respectively. The main representative of the Archaea domain found in biofilm from periodontitis and peri-implantitis sites was Methanobrevibacter oralis. The present results revealed that archaea are present in diseased but not healthy implants. It was also found that archaea were more abundant in periodontitis than in peri-implantitis sites. Hence, the potential role of archaea in peri-implantitis and periodontitis should be taken into consideration.

ß-Defensin Strengthens Antimicrobial Peritoneal Mast Cell Response.

Mast cells (MCs) are engaged in the processes of host defense, primarily via the presence of receptors responsible for the detection of pathogen-associated molecular patterns (PAMPs). Since BDs are exclusively host defense molecules, and MCs can elicit the antimicrobial response, this study is aimed at determining whether BDs might be involved in MC pathogen defense. We found that defensin BD-2 significantly augments the mRNA and protein expression of Toll-like receptors (TLRs) and retinoic acid-inducible gene-I-like receptor (RLR) essential for the detection of viral molecules, i.e., TLR3, TLR7, TLR9, and RIG-I in mature tissue rat peritoneal MCs (PMCs). We established that BD-2 might stimulate PMCs to release proinflammatory and immunoregulatory mediators and to induce a migratory response. Presented data on IgE-coated PMC upon BD-2 treatment suggest that in the case of allergies, there is an enhanced MC immune response and cell influx to the site of the ongoing infection. In conclusion, our data highlight that BD-2 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.

The Response of Tissue Mast Cells to TLR3 Ligand Poly(I:C) Treatment.

Mast cells (MCs) are found mainly at the anatomical sites exposed to the external environment; thus, they are localized close to blood vessels, lymphatic vessels, and a multitude of immune cells. Moreover, those cells can recognize invading pathogens through a range of surface molecules known as pathogen recognition receptors (PRRs), mainly Toll-like receptors (TLRs). MCs are extensively engaged in the control and clearance of bacterial infections, but much less is known about their contribution to antiviral host response as well as pathomechanisms of virus-induced diseases. In the study, we employed in vivo differentiated mature tissue mast cells freshly isolated from rat peritoneal cavity. Here, we demonstrated that rat peritoneal mast cells (rPMCs) express viral dsRNA-specific TLR3 molecule (intracellularly and on the cell surface) as well as other proteins associated with cellular antiviral response: IRF3, type I and II IFN receptors, and MHC I. We found that exposure of rPMCs to viral dsRNA mimic, i.e., poly(I:C), induced transient upregulation of surface TLR3 (while temporarily decreased TLR3 intracellular expression), type II IFN receptor, and MHC I. TLR3 ligand-stimulated rPMCs did not degranulate but generated and/or released type I IFNs (IFN-α and IFNß) as well as proinflammatory lipid mediators (cysLTs), cytokines (TNF, IL-1ß), and chemokines (CCL3, CXCL8). We documented that rPMC priming with poly(I:C) did not affect FcεRI-dependent degranulation. However, their costimulation with TLR3 agonist and anti-IgE led to a significant increase in cysLT and TNF secretion. Our findings confirm that MCs may serve as active participants in the antiviral immune response. Presented data on modulated FcεRI-mediated MC secretion of mediators upon poly(I:C) treatment suggests that dsRNA-type virus infection could influence the severity of allergic reactions.

Curdlan stimulates tissue mast cells to synthesize pro-inflammatory mediators, generate ROS, and migrate via Dectin-1 receptor.

Mast cells (MCs) are engaged in host defense against various pathogens as they are equipped with pattern recognition receptors (PRRs). Among PRRs expressed on MCs, there are also molecules recognizing components of the fungal cell wall, which are able to induce cellular activation and response. However, little information is available concerning the MC activation by various fungal-derived components. The aim of the study was to determine whether curdlan, a model fungal particle of ß-(1,3)-glucan, can directly stimulate tissue MCs. We demonstrated that curdlan triggers MCs to initiate pro-inflammatory response as it activates these cells to synthesize essential pro-inflammatory and/or immunoregulatory factors. We also showed that curdlan serves as a potent chemoattractant for MCs and stimulates those cells to generate reactive oxygen species (ROS). Finally, we documented that curdlan induces MC response via Dectin-1. Our observations support the idea that MCs serve as important sentinels modulating immune response during fungal infection.

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.

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.

The expression of toll-like receptors in peripheral blood mononuclear cells is altered in schizophrenia.

Increasing evidence suggests that in addition to neurochemical abnormalities, various immunological alterations are related to the pathogenesis of schizophrenia. Toll-like receptors (TLRs) actively mediate immune/inflammatory processes and play a pivotal role in damage/danger recognizing. Therefore, the aim of this study was to compare the expression of TLRs in peripheral blood mononuclear cells (PBMCs) in schizophrenic patients with those of healthy subjects. It also measures the metabolic status of the study subjects. Twenty-seven adult European Caucasian patients with paranoid schizophrenia and twenty-nine healthy volunteers were included in this prospective study. qRT-PCR assessed TLR mRNA expression levels. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). The TLR1, TLR2, TLR4, TLR6, and TLR9 expression were down-regulated, in opposite to TLR3 and TLR7 which manifested higher expression in patients with schizophrenia. TLR5 and TLR8 mRNAs did not differ between groups. TLR mRNA expression was highly correlated. Decreased TLR expression may protect against excessive cell stimulation via exogenous and/or endogenous ligands, and may be recognized as a counterbalancing mechanism limiting the excessive development of inflammation.

Adipocytokine Involvement in Innate Immune Mechanisms.

The innate immune response is defined as an immensely complex and sophisticated process aimed at defending the organism against any disturbance in the body homeostasis, including invading pathogens. It requires a close cooperation of a vast amount of different cell types, recognized as inflammatory migrating cells, as well as stationary cells that form tissues. Moreover, innate immune mechanisms require an efficient functioning of various humoral components that exert a significant impact on physiological and pathological processes. Apart from commonly mentioned humoral factors, this group also includes a family of proteins known as adipocytokines that may act as pro- or anti-inflammatory agents or act both ways. Leptin, predominantly characterized as a proinflammatory adipokine, plays a crucial role in endothelium remodeling and regulation, as well as in cell survival and production of numerous cytokines. Adiponectin, similar to leptin, acts on the endothelial cells and the phagocytic properties of immune cells; however, it exerts an anti-inflammatory impact. Resistin has a documented role in the control of angiogenesis and stimulation of proinflammatory mediator generation and release. Furthermore, there are adipokines, ie, visfatin and chemerin, whose participation in the inflammatory processes is ambiguous. This review focuses on the current knowledge on the extensive role of selected adipokines in innate immune response.