Interleukin-12 p40-homodimer production in sensory dorsal root ganglion neurons.
Recently, the reports that sensory nerves contribute to induction and development of peripheral inflammation have been accumulating. Although neuropeptides have been thought to participate in modulation of inflammation, we supposed the involvement of cytokines. Interleukin-12 (IL-12) is a key regulator of cell-mediated immunity. IL-12 is heterodimer cytokine consisting of a p35 and a p40 subunit, but the results that some of immune cell types secrete p40-homodimer have been reported. In this study, we investigated the expression and secretion of IL-12 in mouse sensory neurons in order to evaluate the involvement of sensory neurons in cell-mediated immunity. Expression of IL-12 p40 mRNA was detected and enhanced by interferon-gamma (IFN-gamma), but another subunit of IL-12 p35 mRNA was not detected in sensory dorsal root ganglion (DRG) neurons in culture. IL-12 p40 molecule was detected in DRG neurons by immunocytochemistry. In addition, cultured DRG neurons secreted p40-homodimer that inhibited IL-12-induced STAT4 phosphorylation in T cells. p40 mRNA expression was accumulated in DRG after administration of IFN-gamma into mouse footpad, and this enhancement was eliminated by a cut of sciatic nerve. These results suggest the possibility that p40-homodimer derived from sensory nerves suppresses the excessive peripheral inflammation.
Department of Physiology, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. hikawa_naoshi@isc.sagami-wu.ac.jp
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Hikawa
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Ishikawa
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Takenaka
D000818:Animals; D019771:Axotomy; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D008297:Male; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D021122:Protein Subunits / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050797:STAT4 Transcription Factor; D012584:Sciatic Nerve / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma