Many inflammatory diseases are characterised by persistent and inappropriate neutrophil activation, systemic or localised hypoxia, and bacterial colonisation. Hypoxia represents an important regulator of inflammatory responses because it inhibits neutrophil apoptosis, a process central to the timely resolution of inflammation. Progress in understanding how cells respond to hypoxia has led to the identification of hypoxia-inducible transcription factors (HIFs) and their hydroxylation by the prolyl hydroxylase enzymes. There is now a significant body of data to support a critical role for this HIF pathway in regulating neutrophil function. Moreover, manipulations of specific components of this pathway have very divergent effects on myeloid cell function. In this review, we will discuss the role individual members of the HIF pathway play in regulating key neutrophil functions and the implications this has for the development of effective therapeutic strategies that selectively target inappropriate neutrophil persistence while maintaining a fully competent immune response.

Download full-text PDF

Source
http://dx.doi.org/10.1515/hsz-2012-0335DOI Listing

Publication Analysis

Top Keywords

hif pathway
12
inflammatory responses
8
inappropriate neutrophil
8
neutrophil
5
hypoxia
4
hypoxia hif
4
pathway
4
pathway neutrophilic
4
neutrophilic inflammatory
4
responses inflammatory
4

Similar Publications

Prolyl Hydroxylase Domain protein 2 (PHD2) targets Hypoxia Inducible Factor alpha subunits (HIFα) for oxygen-dependent proline hydroxylation that leads to subsequent ubiquitination and degradation of HIFα. In addition to HIF proteins, growing evidence suggested that PHD2 may exert its multifaceted function through hydroxylase-dependent or independent activities. Given the critical role of PHD2 in diverse biological processes, it is important to comprehensively identify potential PHD2 interacting proteins.

View Article and Find Full Text PDF

A comprehensive proteomic analysis reveals novel inflammatory biomarkers in intracranial aneurysms.

J Proteomics

January 2025

Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang 315010, China. Electronic address:

Inflammation is a complex factor in the pathogenesis of intracranial aneurysms (IA), but its specific cellular inflammatory factors remain uncertain. We collected two cohorts and measured the representation of vascular inflammation-related proteins using the Olink CVD II Vascular Inflammation Panel. We subsequently validated our findings using ELISA and RT-qPCR.

View Article and Find Full Text PDF

[Roles of ferroptosis in the development of diabetic nephropathy].

Zhejiang Da Xue Xue Bao Yi Xue Ban

December 2024

Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.

Article Synopsis
  • Diabetic nephropathy is a serious complication of diabetes that can lead to death, and ferroptosis (an iron-dependent cell death process) plays a role in its progression.
  • AMPK signaling can slow down diabetic nephropathy but excessive activation may cause autophagic death, while Nrf2 and HO-1 pathways can protect against ferroptosis; however, these pathways have complex effects.
  • Other factors like TGF-β1 and specific exosome-related signals also contribute to the development of diabetic nephropathy, suggesting potential new therapeutic targets to prevent or treat this condition.
View Article and Find Full Text PDF
Article Synopsis
  • The interaction between tumor cells and immune cells contributes to the aggressive nature of glioblastoma (GBM), and targeting M2 macrophages can help combat this.
  • The development of a nanoparticle (NP-M-M2pep) that effectively penetrates the blood-brain barrier and targets M2 microglia has shown promise in reducing GBM progression.
  • This approach reprograms M2 microglia into M1 type, enhancing immune response and altering the tumor microenvironment towards a more favorable state for fighting the tumor.
View Article and Find Full Text PDF

Differences in the composition of plasma metabolites and intestinal flora of piglets with different weaning weights revealed by untargeted metabolomics and 16S rRNA gene sequencing.

J Sci Food Agric

January 2025

Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China.

Article Synopsis
  • The study investigates how weaning body weight in piglets affects their growth by analyzing plasma metabolites and gut microbiota.
  • Key findings include a difference in 23 metabolites, with specific lipid molecules being more prevalent in lighter piglets, while metabolic pathways linked to these differences were identified.
  • Additionally, the gut microbiota showed variability, with higher Lactobacillus levels in heavier piglets and specific bacteria serving as biomarkers for weight differences, indicating a correlation between gut health and metabolism.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!