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

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

Research output: Contribution to journalArticle

Abstract

Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, 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 α2 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-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)4630-4638
Number of pages9
JournalJournal of Immunology
Volume174
Issue number8
StatePublished - Apr 15 2005
Externally publishedYes

Fingerprint

Interleukin-13
Interleukin-4
Lung
Genes
Proline
Interleukin-12
Goblet Cells
Hyperplasia
Proteins
Asthma
Collagen Type VI
Real-Time Polymerase Chain Reaction
B-Lymphocytes
Cytokines
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Finkelman, F. D., Yang, M., Perkins, C., Schleifer, K., Sproles, A., Santeliz, J., ... Wills-Karp, M. (2005). Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. Journal of Immunology, 174(8), 4630-4638.

Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. / Finkelman, Fred D.; Yang, Mingyan; Perkins, Charles; Schleifer, Kathleen; Sproles, Alyssa; Santeliz, JoAnna; Bernstein, Jonathan A.; Rothenberg, Marc E.; Morris, Suzanne C.; Wills-Karp, Marsha.

In: Journal of Immunology, Vol. 174, No. 8, 15.04.2005, p. 4630-4638.

Research output: Contribution to journalArticle

Finkelman, FD, Yang, M, Perkins, C, Schleifer, K, Sproles, A, Santeliz, J, Bernstein, JA, Rothenberg, ME, Morris, SC & Wills-Karp, M 2005, 'Suppressive effect of IL-4 on IL-13-induced genes in mouse lung', Journal of Immunology, vol. 174, no. 8, pp. 4630-4638.
Finkelman FD, Yang M, Perkins C, Schleifer K, Sproles A, Santeliz J et al. Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. Journal of Immunology. 2005 Apr 15;174(8):4630-4638.
Finkelman, Fred D. ; Yang, Mingyan ; Perkins, Charles ; Schleifer, Kathleen ; Sproles, Alyssa ; Santeliz, JoAnna ; Bernstein, Jonathan A. ; Rothenberg, Marc E. ; Morris, Suzanne C. ; Wills-Karp, Marsha. / Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. In: Journal of Immunology. 2005 ; Vol. 174, No. 8. pp. 4630-4638.
@article{483825cc5b8543bb868d0c4039768689,
title = "Suppressive effect of IL-4 on IL-13-induced genes in mouse lung",
abstract = "Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, 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 α2 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-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ 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.",
author = "Finkelman, {Fred D.} and Mingyan Yang and Charles Perkins and Kathleen Schleifer and Alyssa Sproles and JoAnna Santeliz and Bernstein, {Jonathan A.} and Rothenberg, {Marc E.} and Morris, {Suzanne C.} and Marsha Wills-Karp",
year = "2005",
month = "4",
day = "15",
language = "English (US)",
volume = "174",
pages = "4630--4638",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Suppressive effect of IL-4 on IL-13-induced genes in mouse lung

AU - Finkelman, Fred D.

AU - Yang, Mingyan

AU - Perkins, Charles

AU - Schleifer, Kathleen

AU - Sproles, Alyssa

AU - Santeliz, JoAnna

AU - Bernstein, Jonathan A.

AU - Rothenberg, Marc E.

AU - Morris, Suzanne C.

AU - Wills-Karp, Marsha

PY - 2005/4/15

Y1 - 2005/4/15

N2 - Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, 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 α2 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-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ 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.

AB - Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, 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 α2 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-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ 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.

UR - http://www.scopus.com/inward/record.url?scp=20144389802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144389802&partnerID=8YFLogxK

M3 - Article

C2 - 15814686

AN - SCOPUS:20144389802

VL - 174

SP - 4630

EP - 4638

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -