Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the resolution of inflammation

Abstract Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.

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Protein S is Protective in Acute Lung Injury by Inhibiting Cell Apoptosis

International Journal of Molecular Sciences ◽

10.3390/ijms20051082 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1082 ◽

Cited By ~ 3

Author(s):

Prince Baffour Tonto ◽

Taro Yasuma ◽

Tetsu Kobayashi ◽

Corina D’Alessandro-Gabazza ◽

Masaaki Toda ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Transgenic Mice ◽

Lung Tissue ◽

Cell Apoptosis ◽

Inflammatory Cell ◽

Protein S ◽

Inflammatory Cell Infiltration ◽

Human Protein ◽

Wild Type

Acute lung injury is a fatal disease characterized by inflammatory cell infiltration, alveolar-capillary barrier disruption, protein-rich edema, and impairment of gas exchange. Protein S is a vitamin K-dependent glycoprotein that exerts anticoagulant, immunomodulatory, anti-inflammatory, anti-apoptotic, and neuroprotective effects. The aim of this study was to evaluate whether human protein S inhibits cell apoptosis in acute lung injury. Acute lung injury in human protein S transgenic and wild-type mice was induced by intratracheal instillation of lipopolysaccharide. The effect of human protein S on apoptosis of lung tissue cells was evaluated by Western blotting. Inflammatory cell infiltration, alveolar wall thickening, myeloperoxidase activity, and the expression of inflammatory cytokines were reduced in human protein S transgenic mice compared to the wild-type mice after lipopolysaccharide instillation. Apoptotic cells and caspase-3 activity were reduced while phosphorylation of extracellular signal-regulated kinase was enhanced in the lung tissue from human protein S transgenic mice compared to wild-type mice after lipopolysaccharide instillation. The results of this study suggest that human protein S is protective in lipopolysaccharide-induced acute lung injury by inhibiting apoptosis of lung cells.

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The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema

Clinical & Experimental Immunology ◽

10.1046/j.1365-2249.2000.01333.x ◽

2000 ◽

Vol 122 (2) ◽

pp. 150-156 ◽

Cited By ~ 16

Author(s):

C. H. Orteu ◽

M. H. A. Rustin ◽

E. O'toole ◽

C. Sabin ◽

M. Salmon ◽

...

Keyword(s):

T Cell ◽

Atopic Eczema ◽

Cell Apoptosis ◽

Resolution Of Inflammation ◽

T Cell Apoptosis

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Radiation-induced strain differences in mouse alveolar inflammatory cell apoptosis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y05-005 ◽

2005 ◽

Vol 83 (1) ◽

pp. 117-122 ◽

Cited By ~ 32

Author(s):

Thomas J O'Brien ◽

Séverine Létuvé ◽

Christina K Haston

Keyword(s):

Cell Apoptosis ◽

Caspase 3 ◽

Inflammatory Cell ◽

Strain Difference ◽

Strain Differences ◽

Inflammatory Cells ◽

Mouse Lung ◽

C3h Mice ◽

Radiation Induced ◽

Mouse Lungs

Whole-thorax irradiation results in the development of the diffuse inflammatory response alveolitis in C3H/HeJ (C3H) mice and a milder alveolitis with fibrosis in C57BL/6J (B6) mice. In this study, we investigate if this mouse strain difference in response to radiation is due to differences in lung inflammatory cell apoptosis. Mice of the C3H and B6 strains were given a radiation dose of 18 Gy to the thorax and the animals were sacrificed at 11 or 18 weeks following exposure or when they were moribund. Active caspase-3 staining was used to identify apoptotic cells in the alveolar space of histological lung sections from the mice. The apoptotic index of B6 mice was greater than that of C3H mice at 11 weeks postirradiation (17.8% of airspace cells vs. 7.8%, p = 0.028) and in mice sacrificed because of illness (27.3% vs. 14.4%, p = 0.036). No C3H mice survived to the later time point. The inflammatory cells undergoing apoptosis in the mouse lungs were morphologically consistent with alveolar macrophages. We conclude that a difference in inflammatory cell apoptosis may contribute to the disparate pulmonary radiation response of these mouse strains.Key words: mouse, lung, radiation, apoptosis, fibrosis, caspase-3.

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Nuclear Factor-κB Regulates Inflammatory Cell Apoptosis and Phagocytosis in Rat Carrageenin-Sponge Implant Model

American Journal Of Pathology ◽

10.1016/s0002-9440(10)63280-4 ◽

2004 ◽

Vol 165 (1) ◽

pp. 115-126 ◽

Cited By ~ 24

Author(s):

Maria Chiara Maiuri ◽

Gianfranco Tajana ◽

Teresa Iuvone ◽

Daniela De Stefano ◽

Guido Mele ◽

...

Keyword(s):

Cell Apoptosis ◽

Inflammatory Cell ◽

Nuclear Factor Κb ◽

Nuclear Factor

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Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study

PLoS ONE ◽

10.1371/journal.pone.0245209 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245209

Author(s):

Yue-Yu Gu ◽

Min Zhang ◽

Huan Cen ◽

Yi-Fan Wu ◽

Zhaoyu Lu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Molecular Docking ◽

Signaling Pathways ◽

Cell Apoptosis ◽

Active Sites ◽

Inflammatory Cell ◽

Specific Treatment ◽

Kidney Injury ◽

Network Pharmacology ◽

Molecular Docking Study

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

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