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Immunobiology

Immunobiology

IF: 2.3
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Evaluation of the anti-inflammatory effects of PI3Kδ/γ inhibitors for treating acute lung injury

Published:5 October 2023 DOI: PMID: 37832501
Wendian Xiong , Lei Jia , Yanfei Cai , Yun Chen , Mingzhu Gao , Jian Jin , Jingyu Zhu

Abstract

Phosphatidylinositol 3-kinase delta (PI3Kδ) and gamma (PI3Kγ) are predominantly located in immune and hematopoietic cells. It is well-established that PI3Kδ/γ plays important roles in the immune system and participates in inflammation; hence, it could be a potential target for anti-inflammatory therapy. Currently, several PI3K inhibitors are used clinically to treat cancers with aberrant PI3K signaling; however, their role in treating acute respiratory inflammatory diseases has rarely been explored. Herein, we investigated the potential anti-inflammatory activities of several pharmacological PI3K inhibitors, including marketed drugs idelalisib (PI3Kδ), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K with preferential α/δ) and the clinical drug eganelisib (PI3Kγ), for treating acute lung injury (ALI). In the lipopolysaccharide-induced RAW264.7 macrophage inflammatory model, the four inhibitors significantly suppressed proinflammatory cytokine expression by inhibiting the PI3K signaling pathway. Oral administration of PI3K inhibitors markedly improved lung injury in a murine model of ALI. PI3K pathway inhibition decreased inflammatory cell infiltration and total?protein levels, as well as reduced the expression of associated lung inflammatory factors. Collectively, all four representative PI3K inhibitors exerted prominent anti-inflammatory properties, indicating that PI3K δ and/or γ inhibition could be ideal targets to treat respiratory inflammatory diseases by reducing the inflammatory response. The findings of the current study provide a new basis for utilizing PI3K inhibitors to treat acute respiratory inflammatory diseases.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
CAL-101 870281-82-6 C22H18FN7O 325 suppliers $18.00-$3603.60
CAL-101 870281-82-6 C22H18FN7O 325 suppliers $18.00-$3603.60
CAL-101 870281-82-6 C22H18FN7O 325 suppliers $18.00-$3603.60
CAL-101 870281-82-6 C22H18FN7O 325 suppliers $18.00-$3603.60
IPI 145 1201438-56-3 C22H17ClN6O 206 suppliers $18.00-$2550.00
IPI 145 1201438-56-3 C22H17ClN6O 206 suppliers $18.00-$2550.00
IPI 145 1201438-56-3 C22H17ClN6O 206 suppliers $18.00-$2550.00
IPI 145 1201438-56-3 C22H17ClN6O 206 suppliers $18.00-$2550.00
IPI-549 1693758-51-8 C30H24N8O2 129 suppliers $24.00-$3450.00
IPI-549 1693758-51-8 C30H24N8O2 129 suppliers $24.00-$3450.00

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