Dependence of IL-4, IL-13, and nematode-induced alterations in murine small intestinal smooth muscle contractility on Stat6 and enteric nerves.
IL-4 and IL-13 promote gastrointestinal worm expulsion in part through effects on nonlymphoid cells, such as intestinal smooth muscle cells. The roles of Stat6 in IL-4-, IL-13-, and parasitic nematode-induced effects on small intestinal smooth muscle contractility were investigated in BALB/c wild-type and Stat6-deficient mice treated with a long-lasting formulation of recombinant mouse IL-4 (IL-4C) or IL-13 for 7 days. Separate groups of BALB/c mice were infected with Nippostrongylus brasiliensis or were drug-cured of an initial Heligmosomoides polygyrus infection and later reinfected. Infected mice were studied 9 and 12 days after inoculation, respectively. Segments of jejunum were suspended in an organ bath, and responses to nerve stimulation and to acetylcholine and substance P in the presence and absence of tetradotoxin, a neurotoxin, were determined. Both IL-4 and IL-13 increased smooth muscle responses to nerve stimulation in wild-type mice, but the effects were greater in IL-13-treated mice and were absent in IL-13-treated Stat6-deficient mice. Similarly, hypercontractile responses to nerve stimulation in H. polygyrus- and N. brasiliensis-infected mice were dependent in part on Stat6. IL-13, H. polygyrus, and N. brasiliensis, but not IL-4, also increased contractility to acetylcholine by mechanisms that involved Stat6 and enteric nerves. These studies demonstrate that both IL-4 and IL-13 promote intestinal smooth muscle contractility, but by different mechanisms. Differences in these effects correlate with differences in the relative importance of these cytokines in the expulsion of enteric nematode parasites.
Zhao
Aiping
A
Nutritional Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA.
McDermott
Joseph
J
Urban
Joseph F
JF
Gause
William
W
Madden
Kathleen B
KB
Yeung
Karla Au
KA
Morris
Suzanne C
SC
Finkelman
Fred D
FD
Shea-Donohue
Terez
T
D000109:Acetylcholine / Q000008:administration & dosage / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000276:immunology / Q000469:parasitology* / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D018793:Interleukin-13 / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007583:Jejunum / Q000276:immunology / Q000294:innervation / Q000469:parasitology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009130:Muscle, Smooth / Q000276:immunology / Q000294:innervation / Q000469:parasitology* / Q000503:physiopathology; D009351:Nematospiroides dubius / Q000502:physiology; D009559:Nippostrongylus / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology*; D013373:Substance P / Q000008:administration & dosage / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D013373:Substance P; D000109:Acetylcholine