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Intestinal Diseases Research Program, Department of Medicine, McMaster University, Hamilton, Ontario L8N3Z5, Canada
T helper
2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal
transducer and activator of transcription 6 (STAT6) are expressed in
the muscularis externa during nematode infection and are candidate
mediators of the associated hypercontractility. To determine the locus
of action of these cytokines, we examined the IL-4- and IL-13-induced
hypercontractility of the isolated muscle cells from STAT6 +/+ and
STAT6 
/ mice. We compared the results with cells isolated from
Trichinella spiralis-infected STAT6 +/+ and STAT6 /
mice. Carbamylcholine chloride (Carbachol) induced the contraction
of jejunal muscle cells in a concentration-dependent manner maximal
contraction (Rmax 26.7 ± 1.9%). Cells from T. spiralis-infected STAT6 / mice showed the hypertrophy (cell
lengths 41.4 ± 0.8 to 89.0 ± 8.7 µm) and
hypercontractility (Rmax 37.5 ± 1.3%) induced by
infection. IL-4R
mRNA was detected in dispersed smooth muscle cells.
Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and
IL-13 enhanced Carbachol-induced muscle contraction (Rmax
35.5 ± 1.9 and 32.4 ± 2.9%, respectively). Incubation of LMMP from STAT6 / mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was
attenuated in STAT6 / mice (P < 0.02). These
results indicate both IL-4 and IL-13 induce hypercontractility of
muscle cells via the STAT6 pathway, and this is the basis for
hypercontractility observed in T. spiralis-infected mice.
intestine; motility; cytokine
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