Dependence of IL-4, IL-13, and Nematode-Induced Alterations in Murine Small Intestinal Smooth Muscle Contractility on Stat6 and Enteric Nerves

• Published in: The Journal of immunology (1950) 2003-07, Vol.171 (2), p.948-954
• Main Authors: Zhao, Aiping, McDermott, Joseph, Urban, Joseph F., Jr, Gause, William, Madden, Kathleen B, Yeung, Karla Au, Morris, Suzanne C, Finkelman, Fred D, Shea-Donohue, Terez
• Format: Article
• Language: English
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - physiology; Animals; Antibodies, Monoclonal - administration & dosage; Drug Administration Schedule; Electric Stimulation; Enteric Nervous System - immunology; Enteric Nervous System - parasitology; Enteric Nervous System - physiopathology; Female; In Vitro Techniques; Injections, Intravenous; Interleukin-13 - administration & dosage; Interleukin-13 - biosynthesis; Interleukin-13 - physiology; Interleukin-4 - administration & dosage; Interleukin-4 - biosynthesis; Interleukin-4 - immunology; Interleukin-4 - physiology; Jejunum - immunology; Jejunum - innervation; Jejunum - parasitology; Jejunum - physiopathology; Mice; Mice, Inbred BALB C; Mice, Knockout; Muscle Contraction - drug effects; Muscle Contraction - immunology; Muscle Contraction - physiology; Muscle, Smooth - immunology; Muscle, Smooth - innervation; Muscle, Smooth - parasitology; Muscle, Smooth - physiopathology; Nematospiroides dubius - physiology; Nippostrongylus - physiology; Recombinant Proteins - administration & dosage; Signal Transduction - drug effects; Signal Transduction - immunology; Signal Transduction - physiology; STAT6 Transcription Factor; Strongylida Infections - immunology; Strongylida Infections - parasitology; Strongylida Infections - physiopathology; Substance P - administration & dosage; Substance P - physiology; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.2.948

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.