Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation.
Ozone (O(3)), a major component of air pollution and a strong oxidizing agent, can lead to lung injury associated with edema, inflammation, and epithelial cell damage. The effects of O(3) on pulmonary immune cells have been studied in various in vivo and in vitro systems. We have shown previously that O(3) exposure of surfactant protein (SP)-A decreases its ability to modulate proinflammatory cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In this report, we exposed THP-1 cells and/or native SP-A obtained from bronchoalveolar lavage of patients with alveolar proteinosis to O(3) and studied cytokine production and NF-kappaB signaling. The results showed 1) exposure of THP-1 cells to O(3) significantly decreased their ability to express TNF-alpha in response to SP-A; TNF-alpha production, under these conditions, was still significantly higher than basal (unstimulated) levels in filtered air-exposed THP-1 cells; 2) exposure of both THP-1 cells and SP-A to O(3) did not result in any significant differences in TNF-alpha expression compared with basal levels; 3) O(3) exposure of SP-A resulted in a decreased ability of SP-A to activate the NF-kappaB pathway, as assessed by the lack of significant increase and decrease of the nuclear p65 subunit of NF-kappaB and cytoplasmic IkappaBalpha, respectively; and 4) O(3) exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1 cell responsiveness, which did not seem to be mediated via the classic NF-kappaB pathway. These findings indicate that O(3) exposure may mediate its effect on macrophage function both directly and indirectly (via SP-A oxidation) and by involving different mechanisms.
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Branislava
B
Janic
Todd M
TM
Umstead
David S
DS
Phelps
Joanna
J
Floros
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004357:Drug Synergism; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D016328:NF-kappa B; D010083:Oxidants, Photochemical; D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone