A possible role of autogenous IFN-beta for cytokine productions in human fibroblasts.
It has been already known that human diploid fibroblasts are able to produce not only high levels of IFN-beta but also various kinds of cytokines by poly rI: poly rC, and some inflammatory cytokines are induced by IFN-beta gene activation. We also obtained similar results. However, in our system, cytokine productions were extremely enhanced by treating the cells with a low dose of type 1 IFN and the priming effects on cytokine productions were blocked by cycloheximide similar to those on IFN-beta productions. Most of cytokines were produced later than IFN-beta and synthesis patterns of their mRNA showed the same phenomena. We made clear that cytokine productions by poly rI: poly rC are mediated by secreted IFN-beta at a protein level using a monoclonal antibody against human IFN-beta. Further, it was shown that intra-cellular IFN-beta which is not secreted might also participate in cytokine productions. Meanwhile, IL-1beta induced various kinds of cytokines in human fibroblasts and production time courses of these cytokines were similar to those of poly rI: poly rC induced cytokines. Although secreted IFN-beta was not detected in IL-1beta stimulated culture, expression of IFN-beta mRNA was augmented. These results showed that priming effects of type 1 IFN on cytokine productions by poly rI: poly rC might not be the direct action, but successive IFN-beta production might be essential in the production processes of other cytokines. Further, it was suggested that inducible IFN-beta might also take part in IL-1beta-induced cytokine productions.
Sano
Emiko
E
Proteios Research, Inc., Basic Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan. sanoe@proteios.co.jp
Ohashi
Kensaku
K
Sato
Yuichiro
Y
Kashiwagi
Masamitsu
M
Joguchi
Atsuhiro
A
Naruse
Norio
N
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007370:Interferon Type I; D007375:Interleukin-1; D012333:RNA, Messenger; D016899:Interferon-beta; D003513:Cycloheximide; D011070:Poly I-C