Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine with growth factor-like properties for monocytes and dendritic cells (DCs). In the present study, serum GM-CSF levels and the activation status of DCs were studied in type 2 diabetes mellitus (T2DM) subjects.
Methods: Study subjects were recruited from the Chennai Urban Rural Epidemiology Study. Healthy controls (n=45) and T2DM patients (n=45) were included in the study. Serum levels of GM-CSF, interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Enumeration of circulating DCs (myeloid [m] and plasmocytoid [p]) and its surface antigen expression were quantified by flow cytometry.
Results: The serum GM-CSF levels were significantly higher among diabetes subjects compared with subjects without diabetes and showed a positive correlation with glycated hemoglobin (r=0.208, P=0.018). The serum GM-CSF levels were lower in subjects on combined insulin and oral hypoglycemic agents (OHA) treatment (1.09 pg/mL) compared with those taking OHA alone (1.9 pg/mL). The increased GM-CSF levels were associated with the activated phenotype of mDCs and pDCs, as determined by up-regulation of the lineage markers.
Conclusion: The activated state of mDCs and pDCs seen among diabetes subjects might be due to the increased levels of GM-CSF and other pro-inflammatory cytokines.
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http://dx.doi.org/10.1089/dia.2011.0182 | DOI Listing |
Int J Mol Sci
December 2024
Department of Physiopathology, Faculty of Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland.
Rheumatoid arthritis (RA), an autoimmune disease with complex pathogenesis, is characterized by an immune imbalance reflected, e.g., in the disturbed cytokines' profile.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA
Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.
Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).
J Interferon Cytokine Res
January 2025
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous promoter. Homozygous Halo-SOCS1 mice () were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein.
View Article and Find Full Text PDFAnesthesiology
January 2025
Department of Neuroradiology, School of Medicine and Health, Technical University of Munich, Germany.
Background: According to the model of the glymphatic system, the directed flow of cerebrospinal fluid (CSF) is a driver of waste clearance from the brain. In sleep, glymphatic transport is enhanced, but it is unclear how it is affected by anesthesia. Animal research indicates partially opposing effects of distinct anesthetics but corresponding results in humans are lacking.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of General Surgery of Otorhinolaryngology Head and Neck, The Sixth Affiliated Hospital, Sun Yat-Sen University, No.26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, China.
Purpose: Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor microenvironment (TME), exhibiting dual roles across various cancer types. Depending on the context, TAMs can either suppress tumor progression and weaken drug sensitivity or facilitate tumor growth and drive therapeutic resistance. This study explores whether targeting TAMs can suppress the progression of head and neck squamous cell carcinoma (HNSCC) and improve the efficacy of chemotherapy.
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