RGS2 attenuates alveolar macrophage damage by inhibiting the Gq/11-Ca<sup>2+</sup> pathway during cowshed PM2.5 exposure, and aberrant RGS2 expression is associated with TLR2/4 activation.

Ma, Zhenhua; Du, Xiaohui; Sun, Yize; Sun, Ke; Zhang, Xiqing; Wang, Lixia; Zhu, Yanbin; Basang, Wangdui; Gao, Yunhang

RGS2 attenuates alveolar macrophage damage by inhibiting the Gq/11-Ca²⁺ pathway during cowshed PM2.5 exposure, and aberrant RGS2 expression is associated with TLR2/4 activation.

Ma, Zhenhua; Du, Xiaohui; Sun, Yize; Sun, Ke; Zhang, Xiqing; Wang, Lixia; Zhu, Yanbin; Basang, Wangdui; Gao, Yunhang.

Afiliación

Ma Z; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China; Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850009, China.
Du X; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
Sun Y; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
Sun K; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
Zhang X; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
Wang L; Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China.
Zhu Y; Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850009, China.
Basang W; Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850009, China. Electronic address: bw0891@163.com.
Gao Y; Department of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China. Electronic address: gaoyunhang@163.com.

Toxicol Appl Pharmacol ; 487: 116976, 2024 Jun.

Article en En | MEDLINE | ID: mdl-38777097

ABSTRACT

ABSTRACT

Staff and animals in livestock buildings are constantly exposed to fine particulate matter (PM2.5), which affects their respiratory health. However, its exact pathogenic mechanism remains unclear. Regulator of G-protein signaling 2 (RGS2) has been reported to play a regulatory role in pneumonia. The aim of this study was to explore the therapeutic potential of RGS2 in cowshed PM2.5-induced respiratory damage. PM2.5 was collected from a cattle farm, and the alveolar macrophages (NR8383) of the model animal rat were stimulated with different treatment conditions of cowshed PM2.5. The RGS2 overexpression vector was constructed and transfected it into cells. Compared with the control group, cowshed PM2.5 significantly induced a decrease in cell viability and increased the levels of apoptosis and proinflammatory factor expression. Overexpression of RGS2 ameliorated the above-mentioned cellular changes induced by cowshed PM2.5. In addition, PM2.5 has significantly induced intracellular Ca2+ dysregulation. Affinity inhibition of Gq/11 by RGS2 attenuated the cytosolic calcium signaling pathway mediated by PLCß/IP3R. To further investigate the causes and mechanisms of action of differential RGS2 expression, the possible effects of oxidative stress and TLR2/4 activation were investigated. The results have shown that RGS2 expression was not only regulated by oxidative stress-induced nitric oxide during cowshed PM2.5 cells stimulation but the activation of TLR2/4 had also an important inhibitory effect on its protein expression. The present study demonstrates the intracellular Ca2+ regulatory role of RGS2 during cellular injury, which could be a potential target for the prevention and treatment of PM2.5-induced respiratory injury.

Asunto(s)

Macrófagos Alveolares; Material Particulado; Proteínas RGS; Receptor Toll-Like 2; Receptor Toll-Like 4; Animales; Proteínas RGS/genética; Proteínas RGS/metabolismo; Material Particulado/toxicidad; Receptor Toll-Like 4/metabolismo; Receptor Toll-Like 4/genética; Ratas; Macrófagos Alveolares/efectos de los fármacos; Macrófagos Alveolares/metabolismo; Bovinos; Receptor Toll-Like 2/metabolismo; Receptor Toll-Like 2/genética; Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo; Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética; Línea Celular; Señalización del Calcio/efectos de los fármacos; Calcio/metabolismo; Apoptosis/efectos de los fármacos; Contaminantes Atmosféricos/toxicidad

Palabras clave

Cowshed; Fine particulate matter; Gq/11; Intracellular Ca(2+); PLCß/IP(3)R; Regulator of G-protein signaling 2

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Alveolares / Proteínas RGS / Receptor Toll-Like 2 / Receptor Toll-Like 4 / Material Particulado Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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