Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1

Abstract ApxI exotoxin is an important virulence factor derived from Actinobacillus pleuropneumoniae that causes pleuropneumonia in swine. Here, we investigate the role of lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), a member of the β2 integrin family, and the involvement of the int...

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Autores principales:	Siou-Cen Li, Yu-Tsen Cheng, Ching-Yang Wang, Jia-Ying Wu, Zeng-Weng Chen, Jyh-Perng Wang, Jiunn-Horng Lin, Shih-Ling Hsuan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/179341b87cb54ba3839993b114444a2d
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spelling	oai:doaj.org-article:179341b87cb54ba3839993b114444a2d2021-12-02T13:48:42ZActinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-110.1038/s41598-021-81290-92045-2322https://doaj.org/article/179341b87cb54ba3839993b114444a2d2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81290-9https://doaj.org/toc/2045-2322Abstract ApxI exotoxin is an important virulence factor derived from Actinobacillus pleuropneumoniae that causes pleuropneumonia in swine. Here, we investigate the role of lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), a member of the β2 integrin family, and the involvement of the integrin signaling molecules focal adhesion kinase (FAK) and Akt in ApxI cytotoxicity. Using Western blot analysis, we found that ApxI downregulated the activity of FAK and Akt in porcine alveolar macrophages (AMs). Preincubation of porcine AMs with an antibody specific for porcine CD18 reduced ApxI-induced cytotoxicity as measured by a lactate dehydrogenase release assay and decreased ApxI-induced FAK and Akt attenuation, as shown by Western blot analysis. Pretreatment with the chemical compounds PMA and SC79, which activate FAK and Akt, respectively, failed to overcome the ApxI-induced attenuation of FAK and Akt and death of porcine AMs. Notably, the transfection experiments revealed that ectopic expression of porcine LFA-1 (pLFA-1) conferred susceptibility to ApxI in ApxI-insensitive cell lines, including human embryonic kidney 293T cells and FAK-deficient mouse embryonic fibroblasts (MEFs). Furthermore, ectopic expression of FAK significantly reduced ApxI cytotoxicity in pLFA-1-cotransfected FAK-deficient MEFs. These findings show for the first time that pLFA-1 renders cells susceptible to ApxI and ApxI-mediated attenuation of FAK activity via CD18, thereby contributing to subsequent cell death.Siou-Cen LiYu-Tsen ChengChing-Yang WangJia-Ying WuZeng-Weng ChenJyh-Perng WangJiunn-Horng LinShih-Ling HsuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Siou-Cen Li Yu-Tsen Cheng Ching-Yang Wang Jia-Ying Wu Zeng-Weng Chen Jyh-Perng Wang Jiunn-Horng Lin Shih-Ling Hsuan Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
description	Abstract ApxI exotoxin is an important virulence factor derived from Actinobacillus pleuropneumoniae that causes pleuropneumonia in swine. Here, we investigate the role of lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), a member of the β2 integrin family, and the involvement of the integrin signaling molecules focal adhesion kinase (FAK) and Akt in ApxI cytotoxicity. Using Western blot analysis, we found that ApxI downregulated the activity of FAK and Akt in porcine alveolar macrophages (AMs). Preincubation of porcine AMs with an antibody specific for porcine CD18 reduced ApxI-induced cytotoxicity as measured by a lactate dehydrogenase release assay and decreased ApxI-induced FAK and Akt attenuation, as shown by Western blot analysis. Pretreatment with the chemical compounds PMA and SC79, which activate FAK and Akt, respectively, failed to overcome the ApxI-induced attenuation of FAK and Akt and death of porcine AMs. Notably, the transfection experiments revealed that ectopic expression of porcine LFA-1 (pLFA-1) conferred susceptibility to ApxI in ApxI-insensitive cell lines, including human embryonic kidney 293T cells and FAK-deficient mouse embryonic fibroblasts (MEFs). Furthermore, ectopic expression of FAK significantly reduced ApxI cytotoxicity in pLFA-1-cotransfected FAK-deficient MEFs. These findings show for the first time that pLFA-1 renders cells susceptible to ApxI and ApxI-mediated attenuation of FAK activity via CD18, thereby contributing to subsequent cell death.
format	article
author	Siou-Cen Li Yu-Tsen Cheng Ching-Yang Wang Jia-Ying Wu Zeng-Weng Chen Jyh-Perng Wang Jiunn-Horng Lin Shih-Ling Hsuan
author_facet	Siou-Cen Li Yu-Tsen Cheng Ching-Yang Wang Jia-Ying Wu Zeng-Weng Chen Jyh-Perng Wang Jiunn-Horng Lin Shih-Ling Hsuan
author_sort	Siou-Cen Li
title	Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
title_short	Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
title_full	Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
title_fullStr	Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
title_full_unstemmed	Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1
title_sort	actinobacillus pleuropneumoniae exotoxin apxi induces cell death via attenuation of fak through lfa-1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/179341b87cb54ba3839993b114444a2d
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Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1

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