Differential proinflammatory responses of colon epithelial cells to SARS-CoV-2 spike protein and <i>Pseudomonas aeruginosa</i> lipopolysaccharide

Abstract Objectives The study aims to compare the proinflammatory responses of colon epithelial cells to two potent virulence factors: lipopolysaccharide (LPS) from Pseudomonas aeruginosa and spike (S) protein of SARS-CoV-2. Both agents are known to induce significant inflammatory responses, leading to severe clinical manifestations. Methods Human colon epithelial cells were treated with S protein and LPS at various time intervals (12, 24, 48, and 72 h). Cell viability was assessed, and the expression levels of key proinflammatory cytokines ( IFN-γ, IL-1β, TNF-α, and IL-6 ) were measured using qRT-PCR. Statistical analyses were conducted to assess the data, incorporating t-tests and linear regression. Results The study found distinct patterns in cytokine expression in response to S protein and LPS. LPS treatment led to a rapid increase in cytokine expression at early time points (12 and 24 h), followed by a decline at later intervals. In contrast, S protein induced a more sustained proinflammatory response, with lower initial cytokine levels that persisted longer, particularly at 48 and 72 h. Conclusions The differential proinflammatory responses observed between S protein and LPS treatments highlight their unique impacts on colon epithelial cells. Specifically, LPS induced an early but transient spike in cytokine levels, suggesting a rapid but short-lived inflammatory response. Conversely, the S protein triggered a prolonged inflammatory reaction, which may contribute to the persistent symptoms seen in COVID-19. The findings provide insights into the molecular mechanisms underlying inflammatory responses in bacterial and viral infections. Understanding these differences can inform therapeutic strategies for conditions like sepsis and COVID-19, leading to targeted treatments that mitigate excessive inflammation and improve patient outcomes.