HB-EGF Synthesized by CD4 T Cells Modulates Allergic Airway Eosinophilia by Regulating IL-5 Synthesis

Farahnak, Soroor; Simon, Leora; McGovern, Toby K.; Chen, Michael; Khazaei, Niusha; Martin, James G.

doi:10.4049/jimmunol.1801686

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…Similar to NGF and other neurotrophins, HB-EGF is synthesized in a premature transmembrane form (pro-HB-EGF) before it is cleaved by numerous metalloproteinases (MMP3, MMP9, ADM9, ADAM10, ADAM12, ADAM17) into its mature, soluble form (215). While the membrane anchored pro-HB-EGF functions as juxtacrine growth factor and receptor for diphtheria toxin in some species, soluble HB-EGF has recently been described to modulate cell migration, differentiation, and inflammatory functions in multiple cell types (216)(217)(218)(219)(220)(221)(222). In addition, HB-EGF enhances neurogenesis in models of ischemic injury and promotes the survival of dopaminergic neurons (223,224) (Figure 2).…”

Section: Hb-egfmentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

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Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer's disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.

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Section: Hb-egfmentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

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“…Therefore, the combination of HBEGF and adipose-derived stem cells may provide a new solution for the treatment of hair loss. Farahnak et al reported that the intrinsic HBEGF expressed by CD4 T cells had immunomodulatory functions in T(H)2 inflammation and airway dysfunction, 46 and the mechanism was mainly to regulate the expression of IL-5 by binding to and inhibiting the inhibitory function of Bcl-6. Yu et al reported that HBEGF prevented the apoptosis of stromal cells by enhancing the activities of antioxidant enzymes SOD, CAT and GPX, inhibiting the activity of Caspase-3 and the expression of Bax, and restoring the mRNA level of Bcl-2 to improve the oxidative stress-mediated decidua injury.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Dogwood Alcohol Extract on Hepatic Ischemia Reperfusion Injury based on Network Pharmacology and Transcriptomic Sequencing

Guo¹,

Liu²,

Liu³

2023

Future Integr Med

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Background and objective: Hepatic ischemia-reperfusion injury (HIRI) is a key factor leading to complications and poor prognosis after hepatobiliary surgery, but its pathogenesis remains unclear. Hence, it is a very necessary discovery the prevention and treatment methods and pathological mechanism of HIRI. Methods:Our animal experiments indicated that two doses of dogwood alcohol extract (DAX) at 5 g/kg and 2.5 g/kg (crude drug/mouse body mass) could significantly reduce serum alamine aminotransferase (AST) and aspartate aminotransferase (ALT) in HIRI mice. The level of these two transaminases determined the pharmacodynamic effect of DAX on HIRI. Next, we used the results of network pharmacology and transcriptome sequencing to obtain important prevention and cure target genes, and applied molecular docking to simulate receptor and ligand binding. Finally, immunohistochemical method was made use of verifying the results.Results: When the model group vs control group, administration group vs model group, set padj < 0.05, | log2FoldChange | >1.0 filter condition, the intersection between the obtained transcriptome sequencing data set and the network pharmacological target was only heparin-binding epidermal growth factor (HBEGF). Then DockThor online software was applied to make loganin and ursolic acid, small molecular compounds contained in DAX, form complexes with HBEGF active sites through hydrogen bonding to interfere with HIRI. Meanwhile, immunohistochemical test results showed that HBEGF expression decreased in the administration group compared with the model group (*P < 0.05).Conclusions: DAX interferes with the occurrence and development of HIRI by down-regulating HBEGF. Our experimental results not only highlight the advantages of traditional Chinese medicine in treating difficult diseases, but also provide a reference for clinical exploration of new methods to prevent and treat HIRI.

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“…To evaluate lung function, we followed methods previously described 21,22 . Mice were sedated with xylazine (8 mg/kg; intraperitoneally) and anesthetized with pentobarbital sodium (30 mg/kg; intraperitoneally).…”

Section: Measurement Of Respiratory Mechanicsmentioning

confidence: 99%

“…BAL fluid processing and analysis were performed as previously published 22 . Following lung mechanics measurements, BAL was performed by instilling 1 mL of cold PBS via the tracheal cannula, with a subsequent recovery of approximately 0.8 mL of fluid by gentle suction.…”

Section: Bronchoalveolar Lavage (Bal) Fluid Analysismentioning

confidence: 99%

Superiority of systemic bleomycin to intradermal HOCl for the study of interstitial lung disease

Morozan,

Joy,

Fujii

et al. 2023

Sci Rep

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Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and multi-organ fibrosis. Interstitial lung disease (ILD) is a complication of SSc and a leading cause of SSc-death. The administration of hypochlorous acid (HOCl) intradermally in the mouse (HOCl-SSc) purportedly shows several features typical of SSc. We studied the model by injecting BALB/c mice daily intradermally with HOCl for 6-weeks, an exposure reported to induce lung fibrosis. On day 42, the skinfold thickness and the dermal thickness were two and three times larger respectively in the HOCl group compared to controls. HOCl treatment did not result in histological features of pulmonary fibrosis nor significant changes in lung compliance. Automated image analysis of HOCl mice lungs stained with picrosirius red did not show increased collagen deposition. HOCl injections did not increase pulmonary mRNA expression of pro-fibrotic genes nor induced the production of serum advanced oxidation protein products and anti-topoisomerase 1 antibodies. Immune cells in bronchoalveolar lavage fluid (BALF) and whole lung digests were not increased in HOCl-treated animals. Since lung fibrosis is proposed to be triggered by oxidative stress, we injected HOCl to Nrf2−/− mice, a mouse deficient in many antioxidant proteins. Lung compliance, histology, and BALF leukocyte numbers were comparable between Nrf2−/− mice and wild-type controls. We conclude that the HOCl-SSc model does not manifest SSc-lung disease.

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HB-EGF Synthesized by CD4 T Cells Modulates Allergic Airway Eosinophilia by Regulating IL-5 Synthesis

Cited by 3 publications

References 39 publications

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

Protective Effect of Dogwood Alcohol Extract on Hepatic Ischemia Reperfusion Injury based on Network Pharmacology and Transcriptomic Sequencing

Superiority of systemic bleomycin to intradermal HOCl for the study of interstitial lung disease

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