Maciej Siedlar

ORCID: 0000-0002-3904-5412
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About
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Research Areas
  • Immune Cell Function and Interaction
  • Immune cells in cancer
  • Immunodeficiency and Autoimmune Disorders
  • Extracellular vesicles in disease
  • Cancer Immunotherapy and Biomarkers
  • T-cell and B-cell Immunology
  • Immune Response and Inflammation
  • Viral Infections and Immunology Research
  • Spondyloarthritis Studies and Treatments
  • MicroRNA in disease regulation
  • Chemokine receptors and signaling
  • Atherosclerosis and Cardiovascular Diseases
  • Cell Adhesion Molecules Research
  • Cardiac Fibrosis and Remodeling
  • Immunotherapy and Immune Responses
  • CAR-T cell therapy research
  • Cancer Cells and Metastasis
  • Nitric Oxide and Endothelin Effects
  • Cancer Research and Treatments
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Platelet Disorders and Treatments
  • Peptidase Inhibition and Analysis
  • Mycobacterium research and diagnosis
  • Proteoglycans and glycosaminoglycans research
  • COVID-19 Clinical Research Studies

Jagiellonian University
2016-2025

Uniwersytecki Szpital Dziecięcy
2016-2024

Collegium Medicum in Bydgoszcz
2020

Institute of Immunology
2002

Ludwig-Maximilians-Universität München
2000

American Heart of Poland
1999

Utrecht University
1998

Nicolaus Copernicus University
1992

In human blood two monocyte populations can be distinguished, i.e., the CD14(++)CD16(-)DR(+) classical monocytes and CD14(+)CD16(+)DR(++) proinflammatory that account for only 10% of all monocytes. We have studied TNF production in these types cells using three-color immunofluorescence flow cytometry on whole peripheral samples stimulated with either LPS or bacterial lipopeptide S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys(4)-OH,trihydrochloride (Pam3Cys)....

10.4049/jimmunol.168.7.3536 article EN The Journal of Immunology 2002-04-01

IL-10 is a unique cytokine because it anti-inflammatory and immunosuppressive. regulated at the level of transcription, but critical motifs relevant transcription factors controlling this gene have remained elusive to date. We now report that sequence -120 bp in human promoter binds Stat3 no other Stat proteins. Mutation motif abrogates LPS-induced trans-activation. Overexpression dominant negative suppresses activity, while wild-type leads an enhancement activity. Our results show Stat3, by...

10.4049/jimmunol.165.3.1612 article EN The Journal of Immunology 2000-08-01

CA-170 is currently the only small-molecule modulator in clinical trials targeting PD-L1 and VISTA proteins – important negative checkpoint regulators of immune activation. The reported therapeutic results to some extent mimic those FDA-approved monoclonal antibodies overcoming limitations high production costs adverse effects latter. However, no conclusive biophysical evidence proving binding hPD-L1 has ever been presented. Using well-known vitro methods: NMR assay, HTRF cell-based...

10.3390/molecules24152804 article EN cc-by Molecules 2019-08-01

Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases men. LOY the most common acquired mutation aberrant clonal expansion cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA RNA sorted- single-cells vivo vitro. analyses sorted cells showed men diagnosed Alzheimer's disease was primarily affected NK whereas prostate cancer patients...

10.1007/s00018-021-03822-w article EN cc-by Cellular and Molecular Life Sciences 2021-04-01

We describe a new class of potent PD-L1/PD-1 inhibitors based on terphenyl scaffold that is derived from the rigidified biphenyl-inspired structure. Using in silico docking, we designed and then experimentally demonstrated effectiveness terphenyl-based scaffolds inhibiting PD-1/PD-L1 complex formation using various biophysical biochemical techniques. also present high-resolution structure PD-L1 with one our most to identify key PD-L1/inhibitor interactions at molecular level. In addition,...

10.1021/acs.jmedchem.1c00957 article EN cc-by Journal of Medicinal Chemistry 2021-07-27

WNT signaling plays an important role in fibrotic processes the heart. Recently, exosomes have been proposed as novel extracellular transporters for proteins. In this study, we analyzed whether WNT3a and WNT5a carried by could activate downstream molecular pathways human cardiac fibroblasts. Exosomes were isolated from conditioned medium of control, WNT3a- WNT5a-producing L cells differential ultracentrifugations. Obtained showed size ranging between 20⁻150 nm expressed exosomal markers...

10.3390/ijms20061436 article EN International Journal of Molecular Sciences 2019-03-21

In the development of PD-L1-blocking therapeutics, it is essential to transfer initial in vitro findings into proper vivo animal models. Classical immunocompetent mice are attractive due high accessibility and low experimental costs. However, unknown whether inter-species differences PD-L1 sequence structure would allow for human-mouse cross applications. Here, we disclose first mouse (m) analyze its similarity human (h) PD-L1. We show that mPD-L1 interacts with hPD-1 provides a negative...

10.1016/j.isci.2020.101960 article EN cc-by iScience 2020-12-25

Immune checkpoint blockade is one of the most promising strategies cancer immunotherapy. However, unlike classical targeted therapies, it currently solely based on expensive monoclonal antibodies, which often inflict immune-related adverse events. Herein, we propose a novel small-molecule inhibitor at clinically relevant immune checkpoint, PD-1/PD-L1. The compound capable disrupting PD-1/PD-L1 complex by antagonizing PD-L1 and, therefore, restores activation T cells similarly to while being...

10.1021/acs.jmedchem.0c01260 article EN cc-by Journal of Medicinal Chemistry 2020-09-16

Cardiac fibrosis is a pathological process associated with the development of heart failure. TGF-β and WNT signaling have been implicated in pathogenesis cardiac fibrosis, however, little known about molecular cross-talk between these two pathways. The aim this study was to examine effect exogenous canonical WNT3a non-canonical WNT5a TGF-β-activated human fibroblasts. We found that induced β-catenin-dependent response, whereas prompted AP-1 activity. triggered profibrotic signatures...

10.3390/ijms221810072 article EN International Journal of Molecular Sciences 2021-09-17

Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity activated macrophages. Macrophages can be for tumor cell killing by microbial products, including lipopolysaccharide (LPS) and various cytokines. Here we report that in contrast to mouse macrophages, human peripheral blood monocytes stimulated with cytokines or LPS failed release NO. Also priming interferon-gamma followed activation did not cause NO secretion. However, responded production stimulation...

10.1002/eji.1830240225 article EN European Journal of Immunology 1994-02-01

Despite progress in surgical techniques and perioperative care, gastrectomy remains a procedure of significant morbidity. Several scoring systems clinical measures have been adopted to predict postoperative complications gastric cancer patients. The aim this study was investigate whether high serum levels interleukin 6 (IL-6) the early period may be prognostic factor morbidity.A group 99 consecutive patients with resectable were enrolled. mean age 62.9 years male/female ratio 72:27. Subtotal...

10.1007/s10120-011-0039-z article EN cc-by-nc Gastric Cancer 2011-04-19

Immune cells may take part in the renin-angiotensin-aldosterone system (RAAS), which plays a pivotal role regulation of vascular tone and blood pressure. The aim study was to analyse expression activity angiotensin-converting enzyme type 1 (ACE1) ACE2 human monocytes (MO) their subsets. highest relative level ACE1-, as well ACE2-mRNA expression, observed CD14(++)CD16(-) (classical) MO. Moreover, these cells, mean almost two times higher than that ACE1-mRNA (11.48 versus 7.073 units,...

10.1111/cei.12612 article EN Clinical & Experimental Immunology 2015-02-24

Tumour-derived microvesicles (TMVs) are important players in tumour progression, modulating biological activity of immune cells e.g. lymphocytes, monocytes and macrophages. This phenomenon is particularly interesting the progression colon cancer, as macrophages this type relevant for recovery processes. In present study, role cancer cell-derived monocyte differentiation profile (polarization) was investigated. Monocyte-derived (MDM) were differentiated vitro presence TMVs obtained from...

10.1186/s12967-016-0789-9 article EN cc-by Journal of Translational Medicine 2016-02-01

The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor (LDNs/PMN-MDSCs). These have been described in both infections cancer are known for their immunosuppressive activity. In the case COVID-19, long-term complications frequently observed (long-COVID). this context, we...

10.3389/fimmu.2021.748097 article EN cc-by Frontiers in Immunology 2021-09-29

Natural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on balance between activating inhibitory receptors. The immune dysregulation observed COVID-19 patients was previously associated with downregulation NK cell numbers function, yet mechanism inhibition functions interplay infected remain largely unknown. In this study we show that SARS-CoV-2 infection airway epithelial can directly influence phenotype microenvironment. were co-cultured...

10.3389/fimmu.2023.1123155 article EN cc-by Frontiers in Immunology 2023-05-23

Abstract Aims Angiotensin (Ang) II signalling has been suggested to promote cardiac fibrosis in inflammatory heart diseases; however, the underlying mechanisms remain obscure. Using Agtr1a-/- mice with genetic deletion of angiotensin receptor type 1 (ATR1) and experimental autoimmune myocarditis (EAM) model, we aimed elucidate role Ang II-ATR1 pathway development heart-specific autoimmunity post-inflammatory fibrosis. Methods results EAM was induced wild-type (WT) by subcutaneous injections...

10.1093/cvr/cvab039 article EN cc-by-nc Cardiovascular Research 2021-02-05

Pediatric Inflammatory Multisystem Syndrome (PIMS-TS), associated with SARS-CoV-2 infection, is a severe complication after COVID-19 in children. It caused by the immune reaction to SARS-CoV-2, and usually appears three six weeks infection. Unfortunately, PIMS causes non-specific symptoms, which makes its diagnosis treatment difficult. In this paper, we propose Fourier Transform InfraRed spectrometry (FTIR) identify chemical changes blood serum of children induced subsequent syndrome. The...

10.1038/s41598-025-88976-4 article EN cc-by-nc-nd Scientific Reports 2025-02-07

Background. Understanding the reason for decrease in atopic dermatitis risk preterm patients may be crucial development of prophylaxis and therapeutic measures. The hypotheses include a change T-helper1/T-helper2/T-helper17 balance, thymus development, intestinal colonization. This study was designed to compare these parameters between term patients. Methods. investigated population comprised 28 19 term-born On 7th day life, cytokine concentrations were assessed, ultrasonographic examination...

10.23822/eurannaci.1764-1489.393 article EN European Annals of Allergy and Clinical Immunology 2025-03-01
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