PMID- 8454952 OWN - NLM STAT- MEDLINE DCOM- 19930422 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 53 IP - 3 DP - 1993 Mar TI - Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis. PG - 279-86 AB - Bronchoalveolar lavage (BAL) cells were isolated from rats 1, 3, and 6 weeks after a single intratracheal instillation of saline, UICC chrysotile asbestos (5 mg), or silica (5 mg). In asbestos-exposed rats, the pulmonary response was characterized by a significant increase in the number of alveolar macrophages (AMs) and the appearance of fibrotic lesions within 1 week. By contrast, mixed macrophage and neutrophil accumulations were observed in the silica group without evidence of fibrosis. Tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS)-stimulated BAL cells from asbestos-treated rats was significantly lower than controls 1 and 3 weeks after exposure. However, by 6 weeks higher levels of TNF-alpha production were noticeable in this group. Decreases in LPS-induced TNF-alpha production were also observed with BAL cells from silica-treated animals at all time points studied. Lower levels of TNF-alpha were not related to decreased BAL cell viability or the presence of a significant proportion of neutrophils in the silica group. Furthermore, biphasic changes in TNF-alpha production seen in the asbestos group were correlated with concomitant decreases (3 weeks) and increases (6 weeks) in levels of TNF-alpha mRNA in AMs. These data indicate that lower levels of TNF-alpha resulted from inhibition at the gene expression level and provide evidence for bidirectional modulation of TNF-alpha production by AMs during inflammatory reactions. FAU - Ouellet, S AU - Ouellet S AD - Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa, Canada. FAU - Yang, H AU - Yang H FAU - Aubin, R A AU - Aubin RA FAU - Hawley, R G AU - Hawley RG FAU - Wenckebach, G F AU - Wenckebach GF FAU - Lemaire, I AU - Lemaire I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Tumor Necrosis Factor-alpha) RN - 1332-21-4 (Asbestos) SB - IM GS - TNF-&agr; MH - Animals MH - Asbestos/*adverse effects MH - Bronchoalveolar Lavage Fluid/cytology MH - Cell Survival MH - Down-Regulation MH - Gene Expression Regulation MH - Macrophages, Alveolar/*metabolism MH - Male MH - Neutrophils/physiology MH - Pulmonary Fibrosis/*etiology/*metabolism MH - Rats MH - Rats, Wistar MH - Tumor Necrosis Factor-alpha/genetics/*metabolism MH - Up-Regulation EDAT- 1993/03/01 00:00 MHDA- 1993/03/01 00:01 CRDT- 1993/03/01 00:00 PHST- 1993/03/01 00:00 [pubmed] PHST- 1993/03/01 00:01 [medline] PHST- 1993/03/01 00:00 [entrez] AID - 10.1002/jlb.53.3.279 [doi] PST - ppublish SO - J Leukoc Biol. 1993 Mar;53(3):279-86. doi: 10.1002/jlb.53.3.279.