Lymphocyte-mediated regulation of beta-endorphin in the myenteric plexus.
Lymphocytes are antinociceptive and can modulate visceral pain perception in mice. Previously, we have shown that adoptive transfer of CD4+ T cells to severe combined immune-deficient (SCID) mice normalized immunodeficiency-related visceral hyperalgesia. Pain attenuation was associated with an increase in beta-endorphin release by T cells and an upregulation of beta-endorphin in the enteric nervous system. In this study, we investigated the relationship between T cells and opioid expression in the myenteric plexus. We examined opioid peptide and receptor expression in the myenteric plexus in the presence and absence of mucosal T cells. We found a positive association between T cells and beta-endorphin expression; this was accompanied by a downregulation of the micro-opioid receptor (MOR). In vitro, T helper (Th) type 1 and type 2 cytokine stimulation of CD4+ T cells or isolation of T cells from in vivo Th-polarized mice did not increase T cell release of beta-endorphin or the induction of beta-endorphin expression in the myenteric plexus. However, exogenous beta-endorphin did upregulate beta-endorphin expression, and both cycloheximide and naloxone methiodide inhibited peptide upregulation. Therefore, our results suggest that nonpolarized CD4+ T cells release beta-endorphin, which, through an interaction with MOR, stimulates an upregulation of beta-endorphin expression in the myenteric plexus. Thus, we propose that the mechanism underlying lymphocyte modulation of visceral pain involves T cell modulation of opioid expression in the enteric nervous system.
Verma-Gandhu
Monica
M
Intestinal Disease Research Programme, McMaster Univ., 1200 Main St., HSC Bldg., Rm. 3N5C, Hamilton, ON, Canada L8N 3Z5. mverma-gandhu@partners.org
Verdu
Elena F
EF
Cohen-Lyons
Daniel
D
Collins
Stephen M
SM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D003106:Colon / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009197:Myenteric Plexus / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D001615:beta-Endorphin / Q000235:genetics / Q000378:metabolism*
D017450:Receptors, Opioid, mu; D001615:beta-Endorphin