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
Zhenhua Ma , Xiaohui Du , Yize Sun , Ke Sun , Xiqing Zhang , Lixia Wang , Yanbin Zhu , Wangdui Basang , Yunhang Gao
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引用次数: 0
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 PLCβ/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.
期刊介绍:
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.