Endoplasmic reticulum stress-induced NLRP3 inflammasome activation as a novel mechanism of polystyrene microplastics (PS-MPs)-induced pulmonary inflammation in chickens

Microplastics (MPs) have attracted growing attention worldwide as an increasingly prevalent environmental pollutant. In addition, chicken meat is currently the most widely consumed kind of poultry in the global market. Consumer demand for chicken is on the rise both at home and abroad. As a result, the safety of chicken raising has also received significant attention. The lungs play an essential role in the physiological activities of chickens, and they are also the most vulnerable organs. Lung injury is difficult to repair after the accumulation of contaminants, and the mortality rate is high, which brings huge economic losses to farmers. The research on the toxicity of MPs has mainly focused on the marine ecosystem, while the mechanisms of toxicity and lung damage in chickens have been poorly studied. Thus, this study explored the effects of exposure to polystyrene microplastics (PS-MPs) at various concentrations for 42 d on chicken lungs. PS-MPs could cause lung pathologies and ultrastructural abnormalities, such as endoplasmic reticulum (ER) swelling, inflammatory cell infiltration, chromatin agglutination, and plasma membrane rupture. Simultaneously, PS-MPs increased the expression of genes related to the heat shock protein family (<i>Hsp60</i>, <i>Hsp70</i>, and <i>Hsp90</i>), ER stress signaling (activating transcription factor 6 (<i>ATF6</i>), <i>ATF4</i>, protein kinase RNA-like ER kinase (<i>PERK</i>), and eukaryotic translation initiation factor 2 subunit α (<i>eIF2α</i>)), pyroptosis-related genes (NOD-‍, LRR- and pyrin domain-containing protein 3 (<i>NLRP3</i>), apoptosis-associated speck-like protein containing a caspase recruitment domain (<i>ASC</i>), interleukin-1β (<i>IL-1β</i>), cysteinyl aspartate-specific proteinase 1 (<i>Caspase1</i>), and gasdermin-D (<i>GSDMD</i>)), and the inflammatory signaling pathway (nuclear factor-‍κB (<i>NF-</i>‍<i>κB</i>), inducible nitric oxide synthase (<i>iNOS</i>), and cyclooxygenase-2 (<i>COX-2</i>)). The above results showed that PS-MP exposure could result in lung stress, ER stress, pyroptosis, and inflammation in broilers. Our findings provide new scientific clues for further research on the mechanisms of physical health and toxicology regarding MPs.