Microglia express Toll-like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose-dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5alpha and E. coli K1 strains. Low levels of fibronectin exerted a synergistic effect on the release of proinflammatory compounds by microglia co-stimulated with agonists for TLR1/2 (Pam(3)CSK(4)) or TLR9 (CpG DNA), but not in combination with the TLR4 agonist lipopolysaccharide (LPS). Phagocytosis of bacterial strains was moderately enhanced when microglia was co-stimulated with high concentrations of fibronectin and one pathogen-derived TLR agonist. In conclusion, fibronectin increased proinflammatory and phagocytotic functions in microglia and partially synergized with microbial TLR agonists.
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http://dx.doi.org/10.1002/glia.20929 | DOI Listing |
Cell Immunol
December 2024
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address:
Background: Dermal and pulmonary fibrosis are the main clinical symptoms of systemic scleroderma (SSc), for which there are no effective therapeutic agents. Tocilizumab is thought to improve the symptoms of fibrosis, but the effect of tocilizumab on dermal fibrosis has not been explored. This study aims to investigate the therapeutic effect of tocilizumab on skin fibrosis by inhibiting CD38 macrophages in the bleomycin-induced SSc mice model.
View Article and Find Full Text PDFSci Rep
January 2025
Nordic Bioscience, Immunoscience, Herlev Hovedgade 205-207, Herlev, 2730, Denmark.
Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects.
View Article and Find Full Text PDFPLoS One
January 2025
VA Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America.
World J Urol
January 2025
Department of Urology, Peking University People's Hospital, Beijing, 100044, China.
Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target.
Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry.
Int Immunopharmacol
December 2024
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Antibody New Drug Research Center, National Cheng Kung University, Tainan, Taiwan. Electronic address:
Background: Post-laminectomy syndrome (PLS) manifests as recurrent chronic back pain, with or without radiating leg pain, affecting 10-40% of patients following laminectomy. While surgical interventions can alleviate recurrent disc herniation or joint instability, medical management of PLS remains challenging due to unsatisfactory outcomes. Epidural fibrosis is a frequent cause of PLS, leading to nerve root tethering and dural sac compression.
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