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Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni
Substance P (SP) regulates interferon-gamma (IFN-gamma) production through interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammation. Using murine schistosomiasis, we evaluated whether SPr expression was subject to immunoregulation. Splenocytes from schistosome-infected mice cul...
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Published in: | The FASEB journal 2001-04, Vol.15 (6), p.950-957 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Substance P (SP) regulates interferon-gamma (IFN-gamma) production through interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammation. Using murine schistosomiasis, we evaluated whether SPr expression was subject to immunoregulation. Splenocytes from schistosome-infected mice cultured for < or =18 h did not express SPr, as determined by quantitative polymerase chain reaction assay. However, exposure to schistosome egg antigen (SEA) for < or =4 h induced strong receptor expression. Experiments using splenocytes fractionated with antibody-coupled, paramagnetic beads showed that induction localized exclusively to T cells. Receptor protein expression was confirmed with Western blot. Interleukin 12 (IL-12) also induced strong T-cell SPr expression. Both SEA and IL-12 remained strong inducers of T-cell SPr in lymphocytes from the IL-12 (p40) and IFN-gamma R double-knockout mouse, which suggested that SEA did not require IL-12 to induce SPr and that both worked independently of IFN-gamma. Splenocytes from wild-type mice cultured with SEA and neutralizing anti-IL-12 monoclonal antibody (mAb) also showed SPr induction. However, anti-Ia mAb inhibited SEA induction of SPR: Thus, SPr is inducible on T cells. SEA induces SPr through interaction with T-cell receptor (TCR), independently of IL-12 and IFN-gamma. IL-12 induces SPr independently of TCR activation and IFN-gamma expression. SP and its receptor, which regulate IFN-gamma production, are probably part of the IL-12-Th1 circuit. |
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ISSN: | 0892-6638 1530-6860 |
DOI: | 10.1096/fj.00-0379 |