title: Air pollution-associated fly ash particles induce fibrotic mechanisms in primary fibroblasts.
abstract: Air pollution is associated with a variety of respiratory and cardiovascular disorders, including fibrosis. To understand the possible molecular mechanisms underlying this observation, we examined the effect of particulate matter on primary fibroblasts, the key regulators of the extracellular matrix. Fly ash collected in an experimental waste incinerator was used as model particles for fine and ultrafine pollution components. Brief treatment of fibroblasts isolated from adult male Wistar rat hearts with fly ash triggered the immediate formation of intracellular reactive oxygen species (ROS). Using phospho-specific antibodies we observed activation of p38 MAP kinase, p44/42 MAP kinase (ERK1/2) and p70(S6) kinase. Prolonged incubation with fly ash increased the expression of collagen 1 and TGF-beta1, but decreased mRNA levels of MMP9 and TNF-alpha. Cell proliferation was inhibited at high concentrations of fly ash. An increase in the level of advanced glycation endproduct (AGE) modification of various cellular proteins after long-term treatment of cultured fibroblasts with fly ash was observed. The results of our study demonstrate that direct activation of fibroblasts by combustion-derived particles is a mechanism that may contribute to the adverse health effects of particulate air pollution.
authors.affiliation: 1. Department of Cardiothoracic Surgery, University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Gursinsky
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ruhs
authors.forename: Ulrich
authors.initials: U
authors.lastname: Friess
authors.forename: Silvia
authors.initials: S
authors.lastname: Diabaté
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
authors.forename: Rolf-Edgar
authors.initials: RE
authors.lastname: Silber
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
mesh_terms: D000393:Air Pollutants / Q000737:chemistry*; D000818:Animals; D002244:Carbon / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D060729:Coal Ash; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts; D005355:Fibrosis / Q000139:chemically induced; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000096:biosynthesis; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052638:Particulate Matter / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000393:Air Pollutants; D060729:Coal Ash; D017127:Glycation End Products, Advanced; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D002244:Carbon; D019893:Ribosomal Protein S6 Kinases; D020928:Mitogen-Activated Protein Kinases