Cigarette smoke alters hyaluronic acid homeostasis in primary human lung fibroblasts

Background: Hyaluronic acid (HA) mediates lung tissue flexibility which is considerably reduced in asthma and COPD. The pro- or anti-inflammatory effect of HA on tissue physiology depends on the length of the HA molecules. Cigarette smoke is a major risk factor for developing COPD and also is linked to asthma severity. The aim of our study was to investigate the effect of cigarette smoke on HA homeostasis by lung fibroblasts. Methods: Primary lung fibroblasts were isolated from lung tissue biopsies obtained from lung donors (controls) as well as from patients with asthma. Cells were incubated in the presence of smoke conditioned medium for 48 h. Gene expression of HA synthase 1 (HAS-1), hyaluronidase-1 (HYAL-1) and of the HA receptors CD44 and RHAMM was assessed by real time PCR. Results: Cigarette smoke significantly reduced mRNA transcription of HAS-1, but induced the gene expression of HYAL-1. These results indicate an elevated HA catabolism in response to cigarette smoke. Furthermore, the expression of both HA receptors CD44 and RHAMM was significantly reduced in cells treated with cigarette smoke conditioned medium. The above described effects were more prominent in cells obtained from patients with asthma as compared to healthy controls. Conclusion: Our results indicate that cigarette smoke induces HA catabolism which may lead to increased inflammation in the lung through low molecular weight HA molecules.