Suppressive effect of IL-4 on IL-13-induced genes in mouse lung.

Abstract	Although IL-4 signals through two receptors, IL-4R alpha/common gamma-chain (gamma(c)) and IL-4R alpha/IL-13R alpha1, and only the latter is also activated by IL-13, IL-13 contributes more than IL-4 to goblet cell hyperplasia and airway hyperresponsiveness in murine asthma. To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR. Only the collagen alpha2 type VI (Ca2T6) gene and three small proline-rich protein (SPRR) genes were reproducibly induced > 4-fold more by IL-13 than by IL-4. Preferential IL-13 gene induction was not attributable to B cells, T cells, or differences in cytokine potency. IL-4 signaling through IL-4R alpha/gamma(c) suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/gamma(c)-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-gamma, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-gamma production does not suppress the Ca2T6 or SPRR genes. Thus, IL-4 induces genes in addition to IL-12 that suppress STAT6-mediated SPRR gene induction. These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma.
Authors	Fred D Finkelman, Mingyan Yang, Charles Perkins, Kathleen Schleifer, Alyssa Sproles, Joanna Santeliz, Jonathan A Bernstein, Marc E Rothenberg, Suzanne C Morris, Marsha Wills-Karp
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 8 Pg. 4630-8 (Apr 15 2005) ISSN: 0022-1767 [Print] United States
PMID	15814686 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References	Collagen Type VI Cornified Envelope Proline-Rich Proteins Cytokines DNA, Complementary DNA-Binding Proteins IL4R protein, human Il4ra protein, mouse Interleukin-13 Interleukin-4 Receptor alpha Subunit Membrane Proteins Proteins Rag2 protein, mouse Receptors, Cell Surface Recombinant Proteins STAT4 Transcription Factor STAT6 Transcription Factor STAT6 protein, human Stat4 protein, mouse Stat6 protein, mouse Trans-Activators V(D)J recombination activating protein 2 Interleukin-4
Topics	Animals Base Sequence Bronchial Hyperreactivity (etiology, genetics, immunology) Collagen Type VI (genetics) Cornified Envelope Proline-Rich Proteins Cytokines (genetics) DNA, Complementary (genetics) DNA-Binding Proteins (deficiency, genetics, metabolism) Female Gene Expression Profiling Gene Expression Regulation (drug effects) Interleukin-13 (genetics, pharmacology) Interleukin-4 (genetics, pharmacology) Interleukin-4 Receptor alpha Subunit Lung (drug effects, immunology, physiopathology) Membrane Proteins Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Proteins (genetics) Receptors, Cell Surface Recombinant Proteins (pharmacology) Reverse Transcriptase Polymerase Chain Reaction STAT4 Transcription Factor STAT6 Transcription Factor Signal Transduction Trans-Activators (deficiency, genetics, metabolism) Transcriptional Activation

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