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Low-density lipoprotein receptor-related protein 6 ablation in macrophages differentially inhibits lung injury-mediated inflammation and metastasis.
Sung, Eun-Ah; Song, SuJeong; Park, Min Hee; Kelly, Lucianna; Harada, Hisashi; Chae, Wook-Jin.
Afiliación
  • Sung EA; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
  • Song S; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
  • Park MH; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
  • Kelly L; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
  • Harada H; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, United States; Phillips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University School of Dentistry, Richmond, VA, United States.
  • Chae WJ; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States; Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, United States; Phillips Institute for Oral Health Research, School of Dentistry, Virginia C
Biochem Biophys Res Commun ; 695: 149441, 2024 02 05.
Article en En | MEDLINE | ID: mdl-38176174
ABSTRACT
Low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor protein for Wnt ligands. Yet, their role in immune cell regulation remains elusive. Here we demonstrated that genetic deletion of LRP6 in macrophages using LysM-cre Lrp6fl/fl (Lrp6MKO) mice showed differential inhibition of inflammation in the bleomycin (BLM)-induced lung injury model and B16F10 melanoma lung metastasis model. Lrp6MKO mice showed normal immune cell populations in the lung and circulating blood in homeostatic conditions. In the BLM-induced lung injury model, Lrp6MKO mice showed a decreased number of monocyte-derived alveolar macrophages, reduced collagen deposition and alpha-smooth muscle actin (αSMA) protein levels in the lung. In B16F10 lung metastasis model, Lrp6MKO mice reduced lung tumor foci. Monocytic and granulocytic-derived myeloid-derived suppressor cells (M-MDSCs and G-MDSCs) were increased in the lung. In G-MDSCs, hypoxia-inducible factor 1α (HIF1α)+ PDL1+ population was markedly decreased but not in M-MDSCs. Taken together, our results show that the role of LRP6 in macrophages is differential depending on the inflammation microenvironment in the lung.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Lesión Pulmonar / Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Lesión Pulmonar / Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos