Particle-induced expression of SF20/IL25 is mediated by reactive oxygen species and NF-κB in alveolar macrophages

Abstract

Bone marrow stroma-derived growth factor (SF20/IL25) regulates proliferation of lymphoid cells. We previously observed the upregulation of SF20/IL25 in alveolar macrophages treated with fine TiO2 particles and in a TiO2 particle-treated animal model. To identify the mechanism behind TiO2 particle-induced expression of SF20/IL25, we examined the dependence of the induction process on reactive oxygen species and on cytokine-mediated signaling transduction. For in vivo studies, TiO2 particles were intratracheally instilled in Sprague-Dawley rats. For in vitro studies, alveolar macrophages obtained from rat bronchoalveolar lavage cells were cultured in the presence of TiO2 particles. The antioxidant N-acetyl-L-cysteine (NAC) was used to block the formation of reactive oxygen species both in vivo and in vitro, and TPCK, SB203580, and GF10923X were used to inhibit signal transduction mediated by nuclear factor (NF)-κB, p38 MAP kinase, and protein kinase C, respectively, in vitro. In TiO2 particle-treated rats, intraperitoneal administration of NAC significantly decreased lung inflammation and attenuated the production of SF20/IL25 mRNA and protein. In TiO2 particle-stimulated alveolar macrophages, the upregulation of SF20/IL25 mRNA expression was abolished by NAC in a dose-dependent manner. The expression of SF20/IL25 mRNA in the stimulated macrophages was dose-dependently attenuated by TPCK, but not by SB203580 or GF10923X. Fine TiO2 particles stimulate alveolar macrophages to produce SF20/IL25 via the NF-κB-dependent generation of reactive oxygen species.