HEAT-SHOCK-PROTEIN INDUCTION PROTECTS HUMAN RESPIRATORY EPITHELIUM AGAINST NITRIC OXIDE-MEDIATED CYTOTOXICITY

Induction of heat shock proteins (HSPs) confers protection against a v ariety of cytotoxic agents. We hypothesized that induction of HSPs wou ld protect cultured human respiratory epithelium against nitric oxide (NO)-mediated injury. Incubation of a human bronchial epithelial cell line (BEAS-2B cells) at 43 degrees C for 1.5 h induced expression of s everal HSPs. Prior induction of HSPs was associated with protection ag ainst the NO-donors S-nitroso-N-acetyl penicillamine and 3-morpholinsy dnonimine. Protection was evident as improved short term survival and improved ability of cells to recover and proliferate after exposure to NO. Prior induction of HSPs also attenuated NO-mediated decreases in cellular ATP levels, but did not decrease nitrotyrosine formation. Spe cific overexpression of HSP-70 by plasmid-directed gene transfer prote cted murine respiratory epithelial cells against S-nitroso-N-acetyl pe nicillamine. We conclude that in cultured human respiratory epithelium induction of HSPs confers protection against NO-mediated cytotoxicity , possibly by preservation of cellular energetics. We also suggest tha t HSP-70 may play a specific role in protection.