Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets.
ABSTRACT 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)
SourceAvailable from: Heqiao Dai
Journal of Interferon & Cytokine Research 01/1995; 15(1):63-70. DOI:10.1089/jir.1995.15.63 · 3.90 Impact Factor
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ABSTRACT: Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.Neuroscience Letters 11/2012; 534. DOI:10.1016/j.neulet.2012.11.011 · 2.06 Impact Factor