Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS-2 inhibition by Trichinella spiralis.
Gastrointestinal nematode infection is known to alter host T cell activation and has been used to study immune and inflammatory reactions in which nitric oxide (NO) is a versatile player. We previously demonstrated that Trichinella spiralis infection inhibits host inducible NO synthase (NOS-2) expression. We now demonstrate that (i) an IL-4 receptor alpha-subunit (IL-4Ralpha)/Stat6-dependent but T cell-independent pathway is the key for the nematode-induced host NOS-2 inhibition; (ii) endogenous IL-4 and IL-13, the only known IL-4Ralpha ligands, are not required for activating the pathway; and (iii) treatment of RAW264.7 cells with parasite-cultured medium inhibits NOS-2 expression but not cyclooxygenase 2 expression. We propose that a yet-unidentified substance is released by the nematode during the host-parasite interaction.
Bian
Ka
K
Department of Integrative Biology and Pharmacology, Institute of Molecular Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX 77030, USA.
Zhong
Meng
M
Harari
Yael
Y
Lai
Mildred
M
Weisbrodt
Norman
N
Murad
Ferid
F
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D017160:Trichinella spiralis / Q000235:genetics / Q000378:metabolism*
D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat
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