Dibutyryl cAMP, prostaglandin E2, and antioxidants protect cultured bovine bronchial epithelial cells from endotoxin.
Acute bronchitis secondary to bacterial infection in the airway is accompanied by an acute inflammatory response composed predominantly of neutrophils. Mucosal injury with denudation of the airway epithelium to basement membrane frequently occurs. We postulated that endotoxin might explain this cytotoxicity and neutrophil influx. To test this hypothesis, bovine bronchial epithelial cells were cultured, and the culture supernatant fluids were evaluated for neutrophil chemotactic activity (NCA) and lactate dehydrogenase (LDH) after exposure to endotoxin. Escherichia coli endotoxin stimulated the release of NCA and LDH in a dose-dependent manner. Because intracellular augmentation of adenosine 3',5'-cyclic monophosphate (cAMP) has anti-inflammatory effects, we postulated that dibutyryl cAMP (DBcAMP) and prostaglandin E2 (PGE2) might modulate the effect of endotoxin. DBcAMP and PGE2 decreased the release of NCA and LDH. Because cAMP might exert its effect by decreasing intracellular release of oxidants, we investigated the capacity of the antioxidants dimethyl sulfoxide (DMSO) and allopurinol to attenuate the effects of endotoxin. DMSO and allopurinol alone or in combination attenuated the effects of endotoxin-induced NCA and LDH release. These data suggest that endotoxin may account for the pathophysiological changes seen with bronchial bacterial infection or endotoxin inhalation and that the inflammatory responses may be attenuated by DBcAMP, PGE2, and antioxidants.
Koyama
S
S
Research Service, Omaha Veterans Administration Medical Center, Nebraska.
Rennard
S I
SI
Claassen
L
L
Robbins
R A
RA
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004926:Escherichia coli; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D004731:Endotoxins; D016209:Interleukin-8; D000493:Allopurinol; D003994:Bucladesine; D015232:Dinoprostone; D004121:Dimethyl Sulfoxide