Abstract
Occupational exposure to crystalline silica (CS) results in a persistent pulmonary inflammatory response that eventually leads to abnormal tissue repair, disability, and death. The inflammatory-immune responses occur in the early stages of CS exposure, and both innate and adaptive immunity are involved. CD4+ T cells play a pivotal role in the pathogenesis of CS-induced pulmonary disease, which has no proven curative therapy. Dihydrotanshinone I (DHI), a natural product isolated from Salvia miltiorrhiza Bunge (Danshen), has anti-inflammatory and immunomodulatory properties. However, whether DHI has a protective effect on CS-induced lung disease, how it influences the Th immune response, and the potential underlying molecular mechanism(s) have not been fully clarified. In this study, DHI treatment of CS-exposed mice reduced the expression of proinflammatory cytokines and the infiltration of immune cells. It significantly ameliorated CS-induced pulmonary inflammation by attenuating T helper (Th)1 and Th17 responses, which were tightly related to the inhibition of STAT1 and STAT3. DHI significantly altered Th2 cytokines but not the Th2 nuclear transcription factor. Furthermore, our study found that DHI treatment also affected regulatory T cell activity in CS-injured mice. Taken together, our findings indicated that DHI could modulate Th responses and alleviate CS-induced pulmonary inflammation, suggesting a novel application of DHI in CS-induced pulmonary disease.
Highlights
Environmental and occupational exposure to crystalline silica (CS) particles represents an unresolved major public health problem affecting large populations on a global scale
CS-induced pulmonary inflammation begins with the activation of the innate immune response, which produces an environment rich in proinflammatory cytokines and chemokines that induce the infiltration of different inflammatory cells, including neutrophils, macrophages, and lymphocytes [4, 5]
To investigate the underlying mechanism of the effect of Dihydrotanshinone I (DHI) on the immune response, we examined the effects of DHI on the proinflammatory transcription factors STAT1 and STAT3, which play crucial roles in the differentiation of T helper (Th) cells [45]
Summary
Environmental and occupational exposure to crystalline silica (CS) particles represents an unresolved major public health problem affecting large populations on a global scale. Long-term inhalation of CS particles causes an occupational lung disease, which is especially prevalent in developing countries [2]. This disease is characterized by persistent lung inflammation and aberrant tissue repair [3]. Because CS particles deposited into the lungs cannot be removed, CS-induced pulmonary inflammation persists and leads to the activation of the adaptive immune response, severe pulmonary injury, and disability and death [6]. Prevention of CS-induced lung disease remains a major clinical challenge in modern society
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