Pro-inflammatory potential of ultrafine particles in mono- and co-cultures of primary cardiac cells.
Inhalation of particulate air pollution has been associated with increased risks for cardiovascular mortality and morbidity, but the underlying mechanisms are still under discussion. One possible pathway may be that inhaled particles cross the air-blood barrier and interact directly with cardiac tissue. The aim of the present study was to examine the pro-inflammatory potential of particles in cardiac cells. Mono- and co-cultures of primary adult male Wistar (Han) rat cardiomyocytes (CMs) and cardiofibroblasts (CFs) were exposed to increasing concentrations of ultrafine (<100nm) carbon black particles (Printex 90). Expression and release of cytokines (IL-6, IL-1beta and TNF-alpha) were measured by using quantitative real-time PCR and ELISA, respectively. Cytotoxicity was estimated by measuring cellular release of lactate dehydrogenase (LDH). A particle concentration-dependent increase in IL-6 release was observed in both CM mono- and co-cultures (EC(50) approximately 57microg/ml). Furthermore, IL-6 levels detected in both control and particle-exposed co-cultures were synergistically increased compared to mono-cultures (10-19-fold, dependent on the exposure). Experiments with contact and non-contact co-cultures indicate that direct cellular contact is of key importance for the enhanced release of IL-6 in co-cultures. An apparent particle-induced release of IL-1beta was only detected in co-cultures. The release of TNF-alpha was low and did not seem notably influenced by particle exposure. Treatment with an IL-1 receptor antagonist apparently eliminated the particle-induced release of IL-6. In conclusion, ultrafine particles have a pro-inflammatory potential in primary cardiac cells. Furthermore, IL-1 seems critical in triggering particle-induced release of IL-6. These pro-inflammatory responses may be elicited when particles are translocated into the pulmonary circulation upon inhalation or administered intravascularly during medical procedures.
Totlandsdal
Annike I
AI
Department of Air Pollution and Noise, Norwegian Institute of Public Health, Nydalen, NO-0403 Oslo, Norway. Annike.Irene.Totlandsdal@fhi.no
Skomedal
Tor
T
Låg
Marit
M
Osnes
Jan-Bjørn
JB
Refsnes
Magne
M
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000209:etiology*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D010316:Particle Size; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D053260:Soot / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000393:Air Pollutants; D053583:Interleukin-1beta; D015850:Interleukin-6; D053260:Soot; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase