| First Author | Beckmann N | Year | 2020 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 318 |
| Issue | 5 | Pages | L864-L872 |
| PubMed ID | 32101016 | Mgi Jnum | J:299481 |
| Mgi Id | MGI:6450229 | Doi | 10.1152/ajplung.00455.2019 |
| Citation | Beckmann N, et al. (2020) IFNgamma and TNFalpha mediate CCL22/MDC production in alveolar macrophages after hemorrhage and resuscitation. Am J Physiol Lung Cell Mol Physiol 318(5):L864-L872 |
| abstractText | Acute lung injury is a major complication of hemorrhagic shock and the required resuscitation with large volumes of crystalloid fluids and blood products. We previously identified a role of macrophage-derived chemokine (CCL22/MDC) pulmonary inflammation following hemorrhage and resuscitation. However, further details regarding the induction of CCL22/MDC and its precise role in pulmonary inflammation after trauma remain unknown. In the current study we used in vitro experiments with a murine alveolar macrophage cell line, as well as an in vivo mouse model of hemorrhage and resuscitation, to identify key regulators in CCL22/MDC production. We show that trauma induces expression of IFNgamma, which leads to production of CCL22/MDC through a signaling mechanism involving p38 MAPK, NF-kappaB, JAK, and STAT-1. IFNgamma also activates TNFalpha production by alveolar macrophages, potentiating CCL22/MDC production via an autocrine mechanism. Neutralization of IFNgamma or TNFalpha with specific antibodies reduced histological signs of pulmonary injury after hemorrhage and reduced inflammatory cell infiltration into the lungs. |
