Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor necrosis factor-alpha.
The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III collagen, but only the Thy-1- population displays class II major histocompatibility complex antigens after stimulation with interferon-gamma and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1- fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -alpha (TNF-alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts. The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment. Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1- subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1- fibroblast membranes and supernatants was completely neutralized by IL 1 alpha-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1- subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.
Phipps
R P
RP
University of Rochester Cancer Center, NY.
Baecher
C
C
Frelinger
J G
JG
Penney
D P
DP
Keng
P
P
Brown
D
D
D000818:Animals; D000954:Antigens, Surface; D015152:Blotting, Northern; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000954:Antigens, Surface; D007375:Interleukin-1; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha