Related Experiment Video
Updated: Jun 16, 2025
10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
3.2K
HIF-1α Promotes Inflammatory Responses in Aspergillus Fumigatus Keratitis by Activating Pyroptosis Through
Hua Yang1, Mengzhu Liu1, Shiqi Song1
1Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao, China.
Investigative Ophthalmology & Visual Science
|June 10, 2025
Summary
Hypoxia-inducible factor-1α (HIF-1α) promotes Aspergillus fumigatus keratitis by worsening inflammation and slowing corneal healing. Inhibiting HIF-1α accelerates repair and reduces disease severity.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Aspergillus fumigatus (A. fumigatus) keratitis is a severe fungal eye infection.
- The role of hypoxia-inducible factor-1α (HIF-1α) in A. fumigatus keratitis is not fully understood.
Purpose of the Study:
- To investigate the expression patterns of HIF-1α in A. fumigatus keratitis.
- To explore the functional significance of HIF-1α in the inflammatory response during A. fumigatus keratitis.
Main Methods:
- Established mouse models and in vitro cell cultures (HCECs, THP-1 macrophages) of A. fumigatus keratitis.
- Utilized HIF-1α inhibition (LW6), Western blot, immunofluorescence, qRT-PCR, clinical scoring, H&E staining, and flow cytometry to assess expression, inflammation, and macrophage polarization.
Main Results:
- HIF-1α expression was significantly upregulated in A. fumigatus keratitis at both mRNA and protein levels.
- HIF-1α inhibition accelerated corneal epithelial repair, reduced macrophage infiltration, modulated macrophage polarization, and attenuated inflammation.
- HIF-1α promotes inflammation by modulating inflammatory mediators and pyroptosis via the caspase-8/GSDMD pathway.
Conclusions:
- HIF-1α plays a pro-inflammatory role in A. fumigatus keratitis.
- Inhibition of HIF-1α demonstrates therapeutic potential for A. fumigatus keratitis by improving corneal healing and reducing inflammation.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
01:24T Cell Types and Functions
964
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
964
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:07MAPK Signaling Cascades
5.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K