K. Huttunen et al., Comparison of mycobacteria-induced cytotoxicity and inflammatory responsesin human and mouse cell lines, INHAL TOXIC, 13(11), 2001, pp. 977-991
Environmental mycobacteria, which are ubiquitous in nature, are also detect
ed in moisture-damaged buildings. Their potential role inducing the adverse
health effects associated with living in moisture damaged buildings requir
es clarification. To establish a model for these studies, we evaluated infl
ammatory responsiveness in different cell lines exposed to environmental my
cobacterial species. Four mycobacterial isolates belonging to Mycobacterium
avium complex and Mycobacterium terrae, recovered from the indoor air samp
led when a moldy building was being demolished, were studied for their cyto
toxicity and ability to stimulate the production of inflammatory mediators
in mouse RAW264.7 and human 28SC macrophage cell lines, and human A549 lung
epithelial cell line. Lipopolysaccharide (LPS) was used as a positive cont
rol. Production of cytokines (tumor necrosis factor alpha, TNF-alpha; inter
leukin 6, IL-6; and interleukin beta, IL-1 beta) was analyzed immunochemica
lly, nitric oxide (NO) by the Griess method, expression of inducible NO syn
thase with Western blot analysis, and cytotoxicity with the MTT test. Both
human and mouse cells produced NO and IL-6 after mycobacterial exposure. Mo
use macrophages also showed production of TNF-alpha induced by both mycobac
teria and LPS, whereas the human cell lines failed to produce TNF-alpha aft
er mycobacterial exposure and the human epithelial cell line also failed to
respond to LPS. Similarly, only mouse macrophages produced IL-1 beta. Myco
bacterial exposure was not cytotoxic to human cells and was only slightly c
ytotoxic to mouse macrophages. The results indicate that environmental myco
bacterial isolates from moldy buildings are capable of activating inflammat
ory mechanisms in both human and murine cells. The human and mouse cell lin
es, however, differ significantly in the grade and type of the responses.