Episodic ozone exposure over two weeks alters pulmonary inflammation and gene expression in Long-Evans rats.

OBJECTIVE

Elevated exposure to ozone (O3) may occur episodically over short windows of time. However, laboratory investigations have consistently shown that repeated ozone exposures produce an adaptation response, reducing the effects of O3 on ventilatory function. To better understand these responses, we developed a rodent model of episodic O3 exposure to characterize differing exposure patterns on pulmonary toxicity.

METHODS

Male, Long-Evans rats were exposed for either two days or two weeks of episodic exposure to 0.4 or 0.8 ppm O3 (4 h/day). Rats in the two-week group were exposed for a total of five nonconsecutive days, with one- to four-day periods of recovery between each exposure. Whole body plethysmography was performed following each exposure. Markers of lung injury and inflammation in the bronchoalveolar lavage fluid were measured, and lung expression of select genes were assessed using qPCR ∼24 h after the final exposure.

RESULTS

Concentration-dependent effects of O3 on breathing parameters and lung injury were observed following two days of exposure. However, these responses were less evident in rats exposed episodically over two weeks. Comparable increases in bronchoalveolar lavage fluid inflammatory cells and cytokine concentrations were observed irrespective of exposure duration. Furthermore, reduced expression of genes involved in neuroendocrine signaling was detected only following two weeks of episodic exposure (Adrb2, Nr3c1, Dusp1, Glccl1).

CONCLUSIONS

Aspects of the adaptation response were still present in rats episodically exposed to O3 over two weeks. On the other hand, O3-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.