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PPARα agonist ameliorates cholestatic liver injury by regulating hepatic macrophage homeostasis.
Int J Biol Macromol
December 2024
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:
Inflammatory response plays an essential role in the pathogenesis of cholestatic liver injury. PPARα agonists have been shown to regulate bile acid homeostasis and hepatic inflammation. However, the immunoregulatory mechanisms through which PPARα agonists ameliorate cholestatic liver injury remain unclear.
View Article and Find Full Text PDFA helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis.
Sci Immunol
December 2024
Department of Immunobiology, Université de Lausanne, Epalinges, Switzerland.
The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using (), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E (PGE) as a major immune regulatory mechanism of heGDH.
View Article and Find Full Text PDFRole of neutrophils in the pathogenesis of Post Kala-azar Dermal Leishmaniasis (PKDL).
PLoS Negl Trop Dis
November 2024
Dept. of Pharmacology, Institute of Post Graduate Medical Education and Research (IPGME&R), Kolkata, India.
Background: Post Kala-azar Dermal Leishmaniasis (PKDL) is a dermal sequel of visceral leishmaniasis (VL), poses a significant threat to the success of ongoing kala-azar elimination program, due to its potential role in sustaining transmission cycles and complicating disease management strategies. In VL, neutrophils have been identified as the 'first line of defence', having multiple roles in disease pathogenesis, but their role in PKDL, if any, still remains elusive; presenting a critical gap in knowledge, and was the aim of this study.
Methodology/principal Findings: In a cohort of PKDL patients, CD66b+ neutrophils were quantified in skin biopsies, followed by immunostaining of FFPE sections to identify activated neutrophils (CD66b+/CD64+) and degranulated (CD66b+/MPO+), along with expression of neutrophil elastase (NE), matrix metalloprotease 9 (MMP9) and collagen I.
ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma.
Int J Mol Sci
November 2024
Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Via Mariano Semmola, 53, 80131 Naples, Italy.
We previously demonstrated that patients with metastatic unresectable stage IIIb-IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.
View Article and Find Full Text PDFThe contribution of the CRP/CD64 axis to renal cancer progression by inducing protumor activation of tumor-associated macrophages.
Clin Transl Immunology
November 2024
Department of Cell Pathology, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.
Objectives: C-reactive protein (CRP) is a well-known acute-phase protein that increases remarkably under various inflammatory conditions and is elevated in patients with malignant tumors. In this study, we investigated the influence of CRP on the tumor microenvironment in clear cell renal cell carcinoma (ccRCC).
Methods: This study explored CRP's role in ccRCC by co-culturing human macrophages with ccRCC cells and employing antibody blocking, RNA sequencing and experiments for functional insights.
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