Serum profiles of matrix metalloproteinases and their tissue inhibitors in long-term pulmonary complication induced by sulfur mustard: Sardasht-Iran Cohort Study (SICS)

Abstract

Sulfur mustard (SM) is a cytotoxic chemical agent which can cause severe irritation and irreversible damages to body tissues. The effect of SM gas on respiratory tract is one of the main causes of short and long term disabling complications. Matrix metalloproteinases (MMPs) have a critical role in controlling extra cellular matrix remodeling and inflammatory responses in lung tissue and are involved in many various chronic pulmonary diseases. The aim of the present study was to evaluate the possible role of MMPs and their endogenous inhibitors in SM induced lung symptoms in exposed subjects 20 years after exposure. Serum level of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 was measured by ELISA and compared between groups of exposed without any symptoms (control group) and with mild or moderate-severe lung complications. MMP-2 and MMP-9 activity was assayed by gelatin zymography method. There was a significant association between serum level of MMP-1 and severity of lung complications in SM exposed groups. MMP-2 activity was decreased in exposed groups with mild lung complications. TIMPs level was not different in exposed and normal groups. We concluded that increased serum levels of MMP-1 and decreased MMP-2 activity may have roles in pathogenesis and persistence of lung complications in SM exposed victims.