Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in murine silicosis.
The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha), derived from macrophages and other cells, may promote mononuclear cell inflammation and fibrosis in pulmonary silicosis. C3H/HeN mice were exposed to control air or to an aerosol of 70 mg/m3 cristobalite silica for 5 h/d for 12 days and examined at 2 and 16 weeks after exposure. This exposure resulted in murine silicosis, as manifested by focal mononuclear cell accumulations, diffuse interstitial fibrosis, lymphoid tissue enlargement, recruitment of inflammatory cells into BAL fluid, and increased total lung collagen. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) with designed primers and membrane hybridization with biotinylated cDNA probes were used to assess the abundance of IL-1beta and TNFalpha mRNA. In situ hybridization with digoxigenin-labeled cDNA probes was used to localize gene expression. Persistent overexpression of both IL-1beta and TNFalpha were found at 2 and 16 weeks in the lungs of silica-exposed mice compared with air-sham control mice. IL-1beta and TNFalpha expression localized to individual mononuclear cells in the alveolar spaces, groups of cells within the aggregate lesions, and scattered mononuclear cells in BALT and lymphoid nodules. Thus, cells producing IL-1beta and TNFalpha appear to be intimately associated with the evolving lesions of silicosis, and the lymphoid tissue of the lung may be important in driving the pathogenesis of this disease.
Davis
G S
GS
Department of Medicine, University of Vermont, Burlington 05405, USA.
Pfeiffer
L M
LM
Hemenway
D R
DR
D000818:Animals; D015870:Gene Expression; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D012829:Silicosis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha