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To explore the involved mechanisms and possible treatments of ambient PM2.5 exposure-induced lung inflammation, this work studied the activity of luteolin, a natural flavonoid which widely presents in many plant species, in murine alveolar macrophage MH S cells exposed to PM2.5. Results showed PM2.5 induced an inflammatory response, as evidenced by significantly increased TNF-α, IL-6, MCP-1 and Rantes levels. and induced iNOS, COX-2, and NF-κB protein expressions in MH-S cells. Moreover, luteolin pre-treatment reduced JAK2 and STAT1 but not STAT3 protein expressions in PM2.5-stimulated MH-S cells. Performing JAK2 inhibitor AG490 further showed reduced TNF-α and IL-6 productions as well as iNOS, COX-2, and NF-κB protein expressions. In addition, although PM2.5 exposure could elevate HO-1 expression basically, luteolin pre-treatment and AG490 administration further significantly enhanced HO-1 expression additionally. Collectively, these results revealed that luteolin inhibits inflammation through suppressing JAK2/STAT1/NF-κB pathway and enhancing HO-1 expression in PM2.5-challenged alveolar macrophage MH-S cells.

To explore the involved mechanisms and possible treatments of ambient PM2.5 exposure-induced lung inflammation, this work studied the activity of luteolin, a natural flavonoid which widely presents in many plant species, in murine alveolar macrophage MH S cells exposed to PM2.5. Results showed PM2.5 induced an inflammatory response, as evidenced by significantly increased TNF-α, IL-6, MCP-1 and Rantes levels. and induced iNOS, COX-2, and NF-κB protein expressions in MH-S cells. Moreover, luteolin pre-treatment reduced JAK2 and STAT1 but not STAT3 protein expressions in PM2.5-stimulated MH-S cells. Performing JAK2 inhibitor AG490 further showed reduced TNF-α and IL-6 productions as well as iNOS, COX-2, and NF-κB protein expressions. In addition, although PM2.5 exposure could elevate HO-1 expression basically, luteolin pre-treatment and AG490 administration further significantly enhanced HO-1 expression additionally. Collectively, these results revealed that luteolin inhibits inflammation through suppressing JAK2/STAT1/NF-κB pathway and enhancing HO-1 expression in PM2.5-challenged alveolar macrophage MH-S cells. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) is a type of severe pulmonary inflammatory disease with high rates of morbidity and mortality. Now, an increasing number of studies suggest that lncRNAs may act as key regulators of the inflammatory response and play a crucial role in the pathogenesis of many inflammatory diseases. Our study firstly explored the function and underlying mechanism of lncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) in regulating the inflammatory response of lipopolysaccharide (LPS)-induced ALI in rats. Methods: The ALI rats were constructed by intratracheal instillation with LPS. Hematoxylin and eosin (HE) for histological examination were performed to detect histopathological changes in the lung tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of cytokines TNF-α, IL-6, and IL-1β in the supernatants of the bronchoalveolar lavage fluid (BALF). Quantitative real-time PCR (qRT-PCR) analysis was employed to assess the expression of MALAT1, miR-146a, TNF-α, IL-6, and IL-1β in lung tissues. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to detect the relationship between MALAT1 and miR-146a. Results: The results revealed that MALAT1 knockdown played a protective role in the LPS-induced ALI rat model. In addition, knockdown of MALAT1 in vitro inhibited LPS-induced inflammatory response in murine alveolar macrophages cell line MH-S and murine alveolar epithelial cell line MLE-12. This study found that MALAT1 acts as a molecular sponge for miR-146a and MALAT1 negatively regulated miR-146a expression. Mechanistically, MALAT1 overexpression alleviated the inhibitory effect of miR-146a on LPS-induced inflammatory response in MH-S. Conclusions: Together, our study provided the first evidence that MALAT1 knockdown could suppress inflammatory response by up-regulating miR-146a in LPS-induced ALI, which provided a potential therapeutic target for the treatment of ALI. [ABSTRACT FROM AUTHOR]