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CXCR2 Activated JAK3/STAT3 Signaling Pathway Exacerbating Hepatotoxicity Associated with Tacrolimus.
Drug Des Devel Ther
January 2025
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Purpose: Tacrolimus could induce hepatotoxicity during clinical use, and the mechanism was still unclear, which posed new challenge for the prevention and treatment of tacrolimus-induced hepatotoxicity. The aim of this study was to investigate the mechanism of tacrolimus-induced hepatotoxicity and provide reference for drug development target.
Methods: In this study, biochemical analysis, pathological staining, immunofluorescent staining, immunohistochemical staining, transcriptomic analysis, Western blotting was used to investigate the mechanism of tacrolimus-induced hepatotoxicity in gene knockout mice and Wistar rats.
Myeloid-Derived Suppressor Cell Accumulation Drives Intestinal Fibrosis through mCCL6/hCCL15 Chemokine-Mediated Fibroblast Activation.
Adv Sci (Weinh)
December 2024
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Intestinal fibrosis, a severe complication of Crohn's disease (CD), is linked to chronic inflammation, but the precise mechanism by which immune-driven intestinal inflammation leads to fibrosis development is not fully understood. This study investigates the role of myeloid-derived suppressor cells (MDSCs) in intestinal fibrosis in CD patients and a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse model. Elevated MDSCs are observed in inflamed intestinal tissues prior to fibrosis and their sustained presence in fibrotic tissues of both CD patients and murine models.
View Article and Find Full Text PDFCXCR2 immunomodulatory therapy protects against microstructural white matter injury and gait abnormalities but does not mitigate deficits of cognition in a preclinical model of cerebral palsy.
J Neurochem
January 2025
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Minimizing central nervous system (CNS) injury from preterm birth depends upon understanding the critical pathways that underlie essential neurodevelopmental and CNS pathophysiology. Signaling by chemokine (C-X-C motif) ligand 1 (CXCL1) through its cognate receptor, CXCR2 [(C-X-C motif) receptor 2] is essential for neurodevelopment. Increased CXCR2 signaling, however, is implicated in a variety of uterine and neuropathologies, and their role in the CNS injury associated with perinatal brain injury is poorly defined.
View Article and Find Full Text PDFInhibition of the chemokine receptors CXCR1 and CXCR2 synergizes with docetaxel for effective tumor control and remodeling of the immune microenvironment of HPV-negative head and neck cancer models.
J Exp Clin Cancer Res
December 2024
Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Background: Relapsed head and neck squamous cell carcinoma (HNSCC) unrelated to HPV infection carries a poor prognosis. Novel approaches are needed to improve the clinical outcome and prolong survival in this patient population which has poor long-term responses to immune checkpoint blockade. This study evaluated the chemokine receptors CXCR1 and CXCR2 as potential novel targets for the treatment of HPV-negative HNSCC.
View Article and Find Full Text PDFTemporal dynamics of neutrophil functions in multiple sclerosis.
Neurobiol Dis
December 2024
Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Department of Neurology, The First People's Hospital of Kashi, Kashi, Xinjiang 844000, China. Electronic address:
Early neuroinflammatory injury plays a crucial role in initiating and progressing multiple sclerosis (MS). Neutrophils are forerunners to neural lesions in MS, yet the temporal alterations of their functions in MS remains unclear. This study demonstrated a positive correlation between circulatory neutrophil counts and disease activity and severity in treatment-naïve MS patients.
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