Cigarette Smoke Extract Reduces VEGF in Primary Human Airway Epithelial Cells

¹ Dept of Medicine, National Jewish Medical and Research Center, Denver, CO

^* To whom correspondence should be addressed. E-mail: chuhw{at}njc.org.

	Abstract

Reduced VEGF has been reported in bronchoalveolar lavage fluid (BALF) and lungs of severe emphysema patients. Airway epithelial cells (AEC) are exposed to various environmental insults like cigarette smoke and bacterial infections, but their direct effect on VEGF production in well-differentiated primary human AEC remains unclear.

We determined the effect of cigarette smoke extract (CSE) alone and in combination with Mycoplasma pneumoniae (Mp) on VEGF production in well-differentiated primary normal human bronchial epithelial (NHBE) and small airway epithelial cells (SAEC) under the air-liquid interface cultures. Secretion and expression of VEGF were determined by ELISA and real-time RT-PCR, respectively. Cell growth, apoptosis, extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase C (PKC) signaling pathways were evaluated to further dissect VEGF regulation under CSE treatment.

CSE significantly reduced VEGF secretion in NHBE and SAEC. In SAEC, Mp alone significantly increased the VEGF, while the presence of CSE attenuated Mp-induced VEGF production. While ERK inhibitor reduced VEGF secretion only in NHBE, a PKC inhibitor significantly decreased VEGF secretion in both NHBE and SAEC.

We conclude that direct CSE exposure significantly reduced VEGF production in well-differentiated primary human AEC, which is in part through modifying ERK1/2 and PKC signaling pathways.