Firsthand cigarette smoke alters fibroblast migration and survival: implications for impaired healing.
Although it is known that high levels of cigarette smoke lead to cell death, little is known about the effects of low-to-moderate levels of smoke components that are found in vivo, such as those experienced by cells in tissues. Clinical studies and experimental data show that smokers heal poorly and are more prone to develop fibrotic diseases. Here we show the effects of first-hand cigarette smoke on fibroblasts, cells that are critically involved in these processes. Using doses of smoke found in the tissues of smokers and a variety of cell and molecular approaches, we show that these doses of cigarette smoke do not cause cell death but rather stimulate fibroblasts to produce stress response and survival proteins such as interleukin-8, PKB/Akt, p53, and p21 that in turn contribute to an increase in cell survival. In addition, smoke-treated cells show a decrease in cell migration, which can be explained by the increased cell adhesion and alterations in cytoskeletal elements. We also show that these levels of smoke cause changes in mitochondrial morphology with a minimum loss of function and these changes are the result of exposure to reactive oxygen species. We conclude that the increase in cell survival may lead to a build-up of connective tissue in the area of a wound, potentially leading to delayed healing and/or fibrosis and that the alterations in the cytoskeleton and in cell adhesion result in inhibition of cell migration, a process that could lead to nonclosure of the wound for lack of proper fibroblast migration to form the healing tissue.
Wong
Lina S
LS
Department of Cell Biology and Neuroscience, University of California-Riverside, Riverside, CA 92521, USA.
Martins-Green
Manuela
M
D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D012907:Smoking / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*