STAT4 signal pathways regulate inflammation and airway physiology changes in allergic airway inflammation locally via alteration of chemokines

Kavita Raman, Mark Kaplan, Cory M. Hogaboam, Aaron Berlin, Nicholas W. Lukacs

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Mice homozygous for the STAT4-null mutation were sensitized to cockroach Ag, challenged intratracheally 21 days later, and compared with STAT4-competent allergic mice. The STAT4-/- mice showed significant decreases in airway hyperreactivity (AHR) and peribronchial eosinophils compared with wild-type controls. In addition, pulmonary levels of chemokines were decreased in the STAT4-/- mice, including CC chemokine ligand (CCL)5, CCL6, CCL11, and CCL17. However, levels of Th2-type cytokines, such as IL-4 and IL-13, as well as serum IgE levels were similar in the two groups. Transfer of splenic lymphocytes from sensitized wild-type mice into sensitized STAT4-/- mice did not restore AHR in the mutant mice. Furthermore, chemokine production and peribronchial eosinophilia were not restored during the cellular transfer experiments. Thus, it appears that STAT4 expression contributes to a type 2 process such as allergen-induced chemokine production and AHR. In additional studies, competent allergic mice were treated with anti-IL-12 locally in the airways at the time of allergen rechallenge. These latter studies also demonstrated a decrease in AHR. Altogether, these data suggest that STAT4-mediated pathways play a role locally within the airway for the exacerbation of the allergen-induced responses.

Original languageEnglish
Pages (from-to)3859-3865
Number of pages7
JournalJournal of Immunology
Volume170
Issue number7
StatePublished - Apr 1 2003

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Chemokines
Signal Transduction
Inflammation
Allergens
CC Chemokines
Cockroaches
Interleukin-13
Eosinophilia
Interleukin-12
Eosinophils
Interleukin-4
Immunoglobulin E
Lymphocytes
Cytokines
Ligands
Lung
Mutation
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

STAT4 signal pathways regulate inflammation and airway physiology changes in allergic airway inflammation locally via alteration of chemokines. / Raman, Kavita; Kaplan, Mark; Hogaboam, Cory M.; Berlin, Aaron; Lukacs, Nicholas W.

In: Journal of Immunology, Vol. 170, No. 7, 01.04.2003, p. 3859-3865.

Research output: Contribution to journalArticle

Raman, Kavita ; Kaplan, Mark ; Hogaboam, Cory M. ; Berlin, Aaron ; Lukacs, Nicholas W. / STAT4 signal pathways regulate inflammation and airway physiology changes in allergic airway inflammation locally via alteration of chemokines. In: Journal of Immunology. 2003 ; Vol. 170, No. 7. pp. 3859-3865.
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