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 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.
Blum
A M
AM
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Metwali
A
A
Crawford
C
C
Li
J
J
Qadir
K
K
Elliott
D E
DE
Weinstock
J V
JV
D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology*; D004195:Disease Models, Animal; D006099:Granuloma / Q000378:metabolism; D015801:Helminth Proteins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000947:Antigens, Helminth; D015801:Helminth Proteins; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C079442:gp50 protein, Schistosoma; D018664:Interleukin-12; D007371:Interferon-gamma