| First Author | Nelin LD | Year | 2022 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 322 |
| Issue | 2 | Pages | R126-R135 |
| PubMed ID | 34984926 | Mgi Jnum | J:330372 |
| Mgi Id | MGI:7257046 | Doi | 10.1152/ajpregu.00140.2021 |
| Citation | Nelin LD, et al. (2022) Cyclooxygenase-2 deficiency attenuates lipopolysaccharide-induced inflammation, apoptosis, and acute lung injury in adult mice. Am J Physiol Regul Integr Comp Physiol 322(2):R126-R135 |
| abstractText | Many lung diseases are caused by an excessive inflammatory response, and inflammatory lung diseases are often modeled using lipopolysaccharide (LPS) in mice. Cyclooxygenase-2 (COX-2) encoded by the Ptgs2 gene is induced in response to inflammatory stimuli including LPS. The objective of this study was to test the hypothesis that mice deficient in COX-2 (Ptgs2(-/-)) will be protected from LPS-induced lung injury. Wild-type (WT; CD1 mice) and Ptgs2(-/-) mice (on a CD1 background) were treated with LPS or vehicle for 24 h. LPS treatment resulted in histological evidence of lung injury, which was attenuated in the Ptgs2(-/-) mice. LPS treatment increased the mRNA levels for tumor necrosis factor-alpha, interleukin-10, and monocyte chemoattractant protein-1 in the lungs of WT mice, and the LPS-induced increases in these levels were attenuated in the Ptgs2(-/-) mice. The protein levels of active caspase-3 and caspase-9 were lower in the LPS-treated lungs of Ptgs2(-/-) mice than in LPS-treated WT mice, as were the number of terminal deoxynucleotide transferase dUTP nick end labeling-positive cells in lung sections. LPS exposure resulted in a greater lung wet-to-dry weight ratio (W/D) in WT mice, suggestive of pulmonary edema, while in LPS-treated Ptgs2(-/-) mice, the W/D was not different from controls and less than in LPS-treated WT mice. These results demonstrate that COX-2 is involved in the inflammatory response to LPS and suggest that COX-2 not only acts as a downstream participant in the inflammatory response, but also acts as a regulator of the inflammatory response likely through a feed-forward mechanism following LPS stimulation. |
