Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets.
Interleukin-6 (IL-6) is a pleiotropic cytokine having several functions, including the regulation of immunologic and inflammatory responses. It is produced by many cell types, including lymphocytes, macrophages, and fibroblasts, and is believed to play a major role in pulmonary fibrosis, a condition resulting from expansion of the fibroblast compartment and the accumulation of extracellular matrices secreted primarily by fibroblasts. Production of IL-6 by lung fibroblasts has been well documented; however, it was not known whether all murine lung fibroblasts secreted IL-6 or only subsets thereof. Previous studies in our laboratory have shown that murine lung fibroblasts can be divided into subpopulations based on Thy 1 expression. These subpopulations, Thy 1+ and Thy 1-, differ in morphology, expression of surface markers, and function. IL-6 mRNA was detected in both Thy 1+ and Thy 1- murine fibroblasts and clones using reverse transcriptase polymerase chain reaction (RT-PCR). Interestingly, semi-quantitative RT-PCR and Northern blot analysis demonstrated that IL-6 mRNA was down-regulated in confluent fibroblast cultures versus cultures in log phase growth. Also, IL-6 activity was detected in the supernatants of murine lung fibroblast lines and clones using an IL-6-dependent hybridoma assay. Hybridoma proliferation was inhibited by the addition of a neutralizing anti-mouse IL-6 antibody, indicating that the activity was indeed due to IL-6. The lung fibroblasts expressed IL-6 receptors on their surface as determined by flow cytometry using a rat anti-mouse IL-6 receptor antibody (15A7).(ABSTRACT TRUNCATED AT 250 WORDS)
Fries
K M
KM
University of Rochester Cancer Center, New York.
Felch
M E
ME
Phipps
R P
RP
D000818:Animals; D002455:Cell Division; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000032:analysis; D019947:Receptors, Interleukin-6; D018800:Thy-1 Antigens / Q000032:analysis*
D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D018800:Thy-1 Antigens