Cytokine modulation of T-lymphocyte activation by intestinal smooth muscle cells.
OBJECTIVE
Interleukin 1beta (IL-beta) and tumor necrosis factor alpha (TNF-alpha) are present in the neuromuscular layers during intestinal inflammation and directly affect intestinal smooth muscle function. We investigated whether IL-1beta and TNF-alpha modulate T-cell activation by murine intestinal smooth muscle cells (ISMCs).


METHODS
alpha- and gamma- actin expression in ISMCs was confirmed using reverse-transcription polymerase chain reaction (RT-PCR). ISMCs were analyzed for class II major histocompatibility complex (MHC), intercellular adhesion molecule 1 (ICAM-1), and B7 before and after exposure to interferon gamma (IFN-gamma; 100 or 1000 U/ mL) in the presence or absence of IL-1beta (10 ng/mL) or TNF-alpha (5 ng/mL) for 72 hours. T-cell proliferation on cytokine-pretreated ISMCs was measured in the absence or presence of anti-B7 antibodies.


RESULTS
In a dose-dependent fashion, IFN-gamma-pretreated ISMCs expressed MHC class II, ICAM-1, and B7-2, and stimulated T-cell proliferation. Pretreatment of ISMCs with IL-1beta and IFN-gamma reduced MHC class II and ICAM-1 expression and inhibited T-cell proliferation. When added with 100 U/mL IFN-gamma, TNF-alpha enhanced MHC class II and ICAM-1 expression on ISMCs and T-cell proliferation. However, TNF-alpha and 1000 U/mL IFN-gamma significantly decreased MHC class II expression and T-cell proliferation. Anti-B7-2 monoclonal antibody but not anti-B7-1 inhibited T-cell proliferative responses by >50%.


CONCLUSIONS
Because IL-1beta, TNF-alpha, and T cells are present in the intestinal muscle layers during inflammation, these cytokines may serve to modulate the activation of T cells in this site.
Hogaboam
C M
CM
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada. hogaboam@path.med.umich.edu
Snider
D P
DP
Collins
S M
SM
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha