| First Author | Shi X | Year | 2021 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 320 |
| Issue | 4 | Pages | L627-L639 |
| PubMed ID | 33625944 | Mgi Jnum | J:304911 |
| Mgi Id | MGI:6515320 | Doi | 10.1152/ajplung.00526.2020 |
| Citation | Shi X, et al. (2021) Reticulocalbin 3 deficiency in alveolar epithelium attenuated LPS-induced ALI via NFkappaB signaling. Am J Physiol Lung Cell Mol Physiol |
| abstractText | Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury-repair process. In the present study, we further observed a marked induction of Rcn3 in the alveolar epithelium during LPS-induced ALI. In vitro alveolar epithelial (MLE12) cells consistently exhibited a significant induction of Rcn3 accompanied with NFkappaB activation in response to LPS exposure. We examined the role of Rcn3 in the alveolar inflammatory response by using mice with a selective deletion of Rcn3 in alveolar epithelial cells upon doxycycline administration. The Rcn3 deficiency significantly blunted the ALI and alveolar inflammation induced by intratracheal LPS instillation but not that induced by an intraperitoneal LPS injection (secondary insult); the alleviated ALI was accompanied with decreases in NFkappaB activation and NLRP3 levels but not in GRP78 and cleaved caspase-3 levels. The studies conducted in MLE12 cells consistently showed that Rcn3 knockdown blunted the activations of NFkappaB signaling and NLRP3-dependent inflammasome upon LPS exposure. Collectively, these findings suggest a novel role for Rcn3 in regulating the alveolar inflammatory response to pulmonary infection via the NFkappaB/NLRP3/inflammasome axis and shed additional light on the mechanism of ARDS/ALI. |
