Differential gene expression associated with inflammation and blood pressure regulation induced by concentrated ambient particle exposure

Abstract

Epidemiological studies have indicated that exposure to particle matter (PM) increased the risk of respiratory and cardiovascular morbidity and mortality. It is suggested that PM smaller than 2.5 μm in aerodynamic diameter (PM_2.5) may contribute to these responses. However, the molecular mechanism is still unknown. To elucidate the changes in molecular level, we investigated the gene expression profile of concentrated ambient particles (CAPs)-exposed rats. Aged F344 rats were exposed with CAPs (594 μg/m³) or clean air 4 h per day for 3 days, and lung and heart tissues were then excised for DNA microarray analysis. Expression profiles related to inflammation and blood pressure regulation revealed differential expression of 7 genes in the lung and that of 3 genes in the heart ventricle. According to the complement activation-associated genes, complement factor B (Bf), complement component 2 and 4a (C4a), and C1 inhibitor genes were up-regulated in CAPs-exposed rat lung. Bf and C4a genes were also up-regulated in the heart. These suggest the treated animal ready for production of these proteins when activation of complement cascade is required. Pro-inflammatory cytokine, interleukin-1β, was also up-regulated in CAPs-exposed rat lung. Gene related with blood pressure regulation (angiotensin I converting enzyme) was also up-regulated in CAPs-exposed rat lung. Negative regulator of blood pressure (neuropeptide Y) was down-regulated in CAPs-exposed rat heart. These results indicate that CAPs may affect respiratory and cardiovascular organs by activation of inflammatory responses and disintegration of blood pressure regulation in early stage of CAPs exposure.

Keywords::

• Gene expression
• microarray analysis
• concentrated ambient particles
• particle matter
• inhalation
• inflammation
• blood pressure

Acknowledgements

The authors express gratitude to Dr. Tadao Suzuki, Ms. Junko Kunimi and Mariko Ochi for their technical support, and Dr. Paul S. Satoh, an adjunct professor at Michigan State University, East Lansing, MI, USA, for his suggestions and review during the preparation of this article.

Declaration of interest

This research was supported in part of the Ministry of Education, Science, Sports and Culture, Japan, Grant-in-Aid for Scientific Research (C), 16510027 and 14580574 to Y.I. and the Ministry of Environment. The authors report no conflicts of interest.