Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity

Abstract

Alveolar macrophage (AM) is a mononuclear phagocyte key to the defense against respiratory infections. To understand AM's role in airway disease development, we examined the influence of Secretoglobin family 1a member 1 (SCGB1A1), a pulmonary surfactant protein, on AM development and function. In a murine model, highthroughput RNA-sequencing and gene expression analyses were performed on purified AMs isolated from mice lacking in Scgb1a1 gene and were compared with that from mice expressing the wild type Scgb1a1 at weaning (4 week), puberty (8 week), early adult (12 week), and middle age (40 week). AMs from early adult mice under Scgb1a1 sufficiency demonstrated a total of 37 up-regulated biological pathways compared to that at weaning, from which 30 were directly involved with antigen presentation, antiviral immunity and inflammation. Importantly, these pathways under Scgb1a1 deficiency were significantly down-regulated compared to that in the age-matched Scgb1a1sufficient counterparts. Furthermore, AMs from Scgb1a1-deficient mice showed an early activation of inflammatory pathways compared with that from Scgb1a1-sufficient mice. Our in vitro experiments with AM culture established that exogenous supplementation of SCGB1a1 protein significantly reduced AM responses to microbial stimuli where SCGB1a1 was effective in blunting the release of cytokines and chemokines (including IL-1b, IL-6, IL-8, MIP-1a, TNF-a, and MCP-1). Taken together, these findings suggest an important role for Scgb1a1 in shaping the AM-mediated inflammation and immune responses, and in mitigating cytokine surges in the lungs.

Quantitative proteomics of hamster lung tissues infected with SARS‐CoV‐2 reveal host factors having implication in the disease pathogenesis and severity

“…Some literature have also reported its altered expression following lung injury and where its absence is marked with the greater inflammatory response. [73][74][75] It is also known to regulate alveolar macrophage-mediated inflammatory response upon virus invasion. 75 However, further studies are required to study its effectiveness and the underlying mechanism(s) associated with virus infection.…”

“…[73][74][75] It is also known to regulate alveolar macrophage-mediated inflammatory response upon virus invasion. 75 However, further studies are required to study its effectiveness and the underlying mechanism(s) associated with virus infection. Further, it suggests the usefulness of the hamster model of SARS-CoV-2 infection in evaluating the therapeutic efficacies of these proteins for COVID-19.…”

Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity

“…Reports have also reported its altered expression following lung injury and where its absence is marked with the greater inflammatory response [39–41]. It is also known to regulate alveolar macrophage and respond to inflammation upon virus invasion [41].…”

“…We identified severe downregulation of Scgb1a1 in the lung tissue post-infection (4dpi), suggesting respiratory distress owing to virus-mediated lung injury. Reports have also reported its altered expression following lung injury and where its absence is marked with the greater inflammatory response [39][40][41]. It is also known to regulate alveolar macrophage and respond to inflammation upon virus invasion [41].…”

Integrative phenotypic and genomic analyses reveal strain-dependent responses to acute ozone exposure and their associations with airway macrophage transcriptional activity

“…Other significant DEGs included Scgb1a1, Cyp1b1, and Mmp9. Scgb1a1 is predominantly produced by club cells but was recently implicated in alveolar macrophage immune responses (55) and has been proposed as a biomarker of O3-induced lung injury in humans (56), while…”