Curcumin inhibits mmp-9 mediated angiogenesis in diffuse parenchymal lung disease

Idiopathic pulmonary fibrosis (IPF), a form of diffuse parenchymal lung disease (DPLD), is marked by honeycombing radiologically and characterized by dysregulated fibrogenesis. The other features include aberrant extracellular matrix (ECM) remodelling and angiogenesis. Hence, the aims of study were to evaluate whether MMP-mediated pathway is involved in angiogenesis and the effect of curcumin thereon in DPLD. Firstly, MMP-9 activity in broncho-alveolar lavage fluid (BALF) from with or without honeycombing patients was investigated by Zymography technique. Then BALF samples were evaluated for TNF-α and MMP-9 levels by Western blot analysis, while tubulogenesis by matrigel and angiogenesis by chick chorioallantoic membrane assays. Our study demonstrates that MMP-9 protein expression and activity levels associated with TNF-α protein expression were higher in the BALF of honeycombing +ve patients in comparison to the honeycombing –ve group suggesting MMP-9 plays a pivotal role in TNF-α-mediated down-stream axis protein expressions followed by tubulogenesis and vascularization for angiogenesis to occur. Incubation of BALF from honeycombing +ve patients with curcumin inhibited MMP-9 activity, and expressions of MMP-9, VEGF, pP38MAPK and Egr-3 molecules associated to angiogenesis. Therefore, Curcumin might have a therapeutic significance for arresting dysregulated angiogenesis in honeycombing +ve DPLD patients.