Induction of inducible nitric oxide synthase and apoptosis by LPS and TNF-α in nasal microvascular endothelial cells

Abstract

Conclusion. This study demonstrates that the co-administration of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α) (LPS/TNF-α) can induce the expression of inducible nitric oxide synthase (iNOS), which results in the generation of apoptosis in cultured human nasal microvascular endothelial cells (HNMECs). Since LPS and TNF-α have been suggested to play an important role in the pathophysiology of nasal disease, we conclude that microvascular leakage may therefore contribute to the inflammatory process in nasal disease, such as allergic rhinitis and asthma. Materials and methods. The HNMECs were obtained from the inferior turbinate and subsequently cultured. The expression of iNOS induced by both the LPS and TNF-α was investigated by fluorescent immunohistochemistry, using confocal laser microscopy. The DNA-binding dye, Hoechist 33342, was also used to analyze the apoptosis in the HNMECs. Results. The fluorescent immunohistochemistory study demonstrated that LPS and TNF-α induced the expression of iNOS in HNMECs. LPS/TNF-α remarkably augmented the expression of iNOS in HNMECs in comparison to stimulation by either LPS or TNF-α alone. LPS/TNF-α also induced apoptosis in HNMECs. 1400W, a highly selective inhibitor of iNOS, inhibited both the expression of iNOS and the apoptosis induced by LPS/TNF-α.

• Lipopolysaccharide
• cytokines
• nitric oxide
• microvascular leakage
• Hoechst 33342
• allergic rhinitis