Idiopathic pulmonary fibrosis (IPF) is a progressive and typically fatal lung disease for which no effective therapy has been identified. The disease is characterized by excessive collagen deposition, possibly in response to dysregulated wound healing. Mediators normally involved in would healing induce proliferation of fibroblasts and their differentiation to myofibroblasts that actively secrete collagen. Curcumin, a polyphenolic compound from turmeric, has been shown to exert a variety of biological effects. Effects on IPF and associated cell types remain unclear, however. We accordingly tested the ability of curcumin to inhibit proliferation and differentiation to myofibroblasts by human lung fibroblasts, including those from IPF patients. To further examine the potential usefulness of curcumin in IPF, we examined its ability to reduce fibrosis in bleomycin-treated mice. We show that curcumin effectively reduces profibrotic effects in both normal and IPF fibroblasts in vitro and that this reduction is accompanied by inhibition of key steps in the transforming growth factor-β (TGF-β) signaling pathway. In vivo, oral curcumin treatment showed no effect on important measures of bleomycin-induced injury in mice, whereas intraperitoneal curcumin administration effectively inhibited inflammation and collagen deposition along with a trend toward improved survival. Intraperitoneal curcumin reduced fibrotic progression even when administered after the acute bleomycin-induced inflammation had subsided. These results encourage further research on alternative formulations and routes of administration for this potentially attractive IPF therapy.

Background: While glucocorticoids are currently the most effective therapy for asthma, associated side effects limit enthusiasm for their use. Peroxisome proliferator-activated receptor-γ (PPAR-γ) activators include the synthetic thiazolidinediones (TZDs) which exhibit anti-

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PPARs, most notably PPAR-γ, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-γ and its ligands in deactivating alveolar macrophages—thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus—while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-γ responses play in specific lung diseases.

Fibrosis of the lung is a common endpoint for a variety of diseases. Current available treatments have been mostly ineffective. Proliferation of pulmonary fibroblasts, enhanced production of extracellular matrix components by these cells, and differentiation of fibroblasts to myofibroblasts results in tissue fibrosis. Curcumin, a component of the widely used Ayurvedic compound turmeric, is a potent biological molecule. Numerous studies have characterized its effects on a wide variety of cellular processes and diseases. Its potential role as a therapy for pulmonary fibrosis, however, remains undefined. In this study, we show that treatment of both normal human lung fibroblasts and those obtained from patients with idiopathic interstitial pneumonias (IIPs) results in inhibition of proliferative responses and induces cell cycle arrest. In addition, curcumin inhibits transforming growth factor (TGF)‐β1‐induced myofibroblast differentiation and collagen production. The effects of curcumin were demonstrated to occur, in part, through binding and activation of the nuclear receptor, peroxisome proliferator‐activated receptor‐γ (PPAR‐γ). These observations suggest a role for curcumin as a novel agent in the treatment of fibrotic lung diseases. Supported by NIH Grants HL70068, HL57243, and PO50HL60289.