Keratinocytes Counteract UVB-Induced Immunosuppression in Mice through HIF-1a Signaling

Faßbender, Sonja; Sondenheimer, Kevin; Majora, Marc; Opitz, Friederike V.; Pollet, Marius; Haarmann‐Stemmann, Thomas; Krutmann, Jean; Weighardt, Heike

doi:10.1016/j.jid.2021.07.185

Cited by 7 publications

(5 citation statements)

References 60 publications

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“…Thus, we comprehensively analyzed the immune infiltration of ACP. Our research found that ICI levels in ACP were positively correlated with HIF-1α, which proved that patients with high HIF-1α expression had more active immune responses, which was consistent with the HIF-1α-counteracted immunosuppression reported by Sonja ( 38 ). Hence, a high expression of HIF-1α and milder clinical symptoms in ACP patients may be achieved by increasing the level of adaptive immune response.…”

Section: Discussionsupporting

confidence: 90%

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

et al. 2022

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Craniopharyngiomas (CPs) are histologically benign tumors located in the sellar–suprasellar region. Although the transcriptome development in recent years have deepened our knowledge to the tumorigenesis process of adamantinomatous craniopharyngioma (ACP), the peritumoral immune infiltration of tumor is still not well understood. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify different gene modules based on clinical characteristics and gene expression, and then, the protein–protein interaction (PPI) network with the Cytohubba plug-in were performed to screen pivotal genes. In addition, immune cell infiltration (ICI) analysis was used to evaluate the immune microenvironment of ACP patients. In total, 8,568 differential expression genes were identified based on our datasets and two microarray profiles from the public database. The functional enrichment analysis revealed that upregulated genes were mainly enriched in immune-related pathways while downregulated genes were shown in the hormone and transduction of signaling pathways. The WGCNA investigated the most relevant modules, and 1,858 hub genes was detected, from which the PPI network identified 14 pivotal genes, and the Hypoxia-inducible factor 1-alpha (HIF-1α) pathway including four critical genes may be involved in the development of ACP. Moreover, naïve CD4+ and CD8+ T cells were decreased while specific subtypes of T cells were significantly increased in ACP patients according to ICI analysis. Validation by immunofluorescence staining revealed a higher expression of HIF-1α in ACP (ACP vs. control) and adult-subtype (adult vs. children), suggesting a possible state of immune system activation. Notably, children with low HIF-1α scores were related to the hypothalamus involvement and hydrocephalus symptoms. In this study, we successfully identified HIF-1α as a key role in the tumorigenesis and development of ACP through comprehensive integrated analyses and systematically investigated the potential relationship with immune cells in ACP. The results may provide valuable resources for understanding the underlying mechanisms of ACP and strengthen HIF-1α as a potential immunotherapeutic target in clinical application.

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Section: Discussionsupporting

confidence: 90%

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

et al. 2022

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“…Adaptation to hypoxia environment is mainly regulated through hypoxia-inducible factor 1 (HIF-1α), which is an environmental sensor orchestrating the adaptation to environmental changes [ 23 ]. Under hypoxia environment, HIF-1α subunit is stabilized, allowing translocation to the nucleus, heterodimerization, and activation of gene pathways that minimize oxygen consumption, reduce reactive oxygen species (ROS), and restore oxygen delivery [ 24 ]. Previous studies have indicated that HIF-1α can promote the activation of NLRP3 inflammasome, facilitate the activation of pyroptosis [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Zhang,

Huo,

et al. 2024

Eur J Med Res

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Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.

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“…This might result from NRF2 activation, which was reported to promote HIF1A gene expression and HIF1-α stability [ 30 ]. HIF1-α can translocate to the nucleus and transcribe hypoxic adaptation genes, such as HO-1 [ 13 ]. Moreover, HO-1 and NQO-1 protein expressions were significantly induced by the supplement of AC extract.…”

Section: Resultsmentioning

confidence: 99%

“…DLD not only associates with α-keto acid dehydrogenase, a regulator of ROS, but also metabolizes α-lipoic acid, which activates two cytoprotective proteins, NRF2 and HO-1 [ 12 ]. In addition, under hypoxic conditions and UVB exposure, hypoxia-inducible factor 1 alpha (HIF1-α) is stabilized by NRF2 activation, binds to hypoxia-responsive elements in the nucleus, and initiates the transcription of target genes such as HO-1 [ 13 ]. Therefore, regulation of the NRF2 signaling pathway has the potential to alleviate UVB-induced oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Anemopsis californica Attenuates Photoaging by Regulating MAPK, NRF2, and NFATc1 Signaling Pathways

et al. 2021

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Long-term exposure of the skin to solar radiation causes chronic inflammation and oxidative stress, which accelerates collagen degradation. This contributes to the formation of wrinkles and dark spots, skin fragility, and even skin cancer. In this study, Anemopsis californica (AC), a herb from North America that is well known for treating microorganism infection and promoting wound healing, was investigated for its photoprotective effects. The biological effects of AC were studied on two in vitro models, namely, lipopolysaccharide (LPS)-induced macrophages and ultraviolet B (UVB)-irradiated dermal fibroblasts, to characterize its underlying molecular mechanisms. The results showed that AC decreased the mRNA levels of inflammatory mediators in sensitized macrophages, including cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Moreover, AC alleviated UVB-induced photoaging in dermal fibroblasts by restoring procollagen synthesis. This resulted from the regulation of excessive reactive oxygen species (ROS) by AC, which was mediated by the activation of the antioxidative system nuclear factor erythroid 2-related factor 2 (NRF2). AC also alleviated oxidative stress and inflammatory responses by inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and interfering with the nuclear translocation of the immune regulator nuclear factor of activated T-cells 1 (NFATc1). In conclusion, the protective effects of AC on skin cellular components suggested that it has the potential for use in the development of drugs and cosmetics that protect the skin from UVB-induced chronic inflammation and aging.

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Keratinocytes Counteract UVB-Induced Immunosuppression in Mice through HIF-1a Signaling

Cited by 7 publications

References 60 publications

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats

Anemopsis californica Attenuates Photoaging by Regulating MAPK, NRF2, and NFATc1 Signaling Pathways

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