Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 322, Issue 2, Pages R126-R135Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00140.2021
Keywords
cytokines; inflammation; prostaglandins; pulmonary edema; pulmonary function
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This study found that COX-2 is involved in the inflammatory response to LPS-induced lung injury and may act as a regulator of the inflammatory response through a feed-forward mechanism following LPS stimulation.
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 inflam-matory 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 -a, 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.
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