IL-1, IL-6, and PDGF mRNA expression in alveolar cells following stimulation with a tobacco-derived antigen.
To test the hypothesis that inflammatory cytokine production might be an early event in the development of the disease associated with smoking, we used alveolar cells from healthy nonsmokers stimulated with TGP as a model system. TGP, a phenol-rich glycoprotein which is present in tobacco leaves and cigarette smoke condensate, activates the immune system. It stimulates polyclonal B cell differentiation, induces primarily an IgE response, and activates human leukocytes to produce IL-1. Using in situ nucleic acid hybridization we show that the steady-state levels of IL-1 alpha, IL-1 beta, IL-6, platelet-derived growth factor (PDGF)-A, and PDGF-B mRNAs are consistently elevated in the alveolar cells of all donors following TGP stimulation. The kinetics of mRNA expression suggest that IL-1 alpha and IL-1 beta mRNAs are independently regulated in alveolar cells, while the regulation of PDGF-A and PDGF-B mRNA seems to be similar. The activated cells also synthesize elevated levels of IL-1 and IL-6. These findings lend support to the suggestion that some clinical consequences of smoking might be initiated and enhanced by the production of inflammatory cytokines. Moreover, IL-6 could also activate a polyclonal B cell response, which could lead to the synthesis of autoantibodies and thus cause immune-mediated tissue injury.
Francus
T
T
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Romano
P M
PM
Manzo
G
G
Fonacier
L
L
Arango
N
N
Szabo
P
P
D000941:Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004731:Endotoxins / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D010947:Plants, Toxic; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D014026:Nicotiana / Q000276:immunology*
D000941:Antigens; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger