Abstract
Resistin-like molecule (RELM)-beta is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-beta has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM-beta is strongly induced by diverse allergens and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism. To understand the in vivo role of RELM-beta, we delivered recombinant murine RELM-beta intratracheally to naïve mice. RELM-beta induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM-beta was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM-beta had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM-beta had fibroblast motogenic activity. These results identify RELM-beta as a Th2-associated cytokine with potent inflammatory and remodeling activity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Allergens / immunology*
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Allergens / metabolism
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Animals
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Asthma / immunology
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Asthma / metabolism
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Bronchoalveolar Lavage Fluid / cytology
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Bronchoalveolar Lavage Fluid / immunology
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Cell Movement
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Collagen / metabolism
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Female
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Goblet Cells / immunology
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Hormones, Ectopic / genetics
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Hormones, Ectopic / immunology*
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Hormones, Ectopic / pharmacology
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Intercellular Signaling Peptides and Proteins
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Interleukin-13 / metabolism
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Interleukin-4 / metabolism
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Lung / immunology*
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Lung / metabolism
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Lung / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Mutant Strains
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NIH 3T3 Cells
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Pneumonia / immunology*
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Pneumonia / metabolism
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Pneumonia / pathology
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Respiratory Mucosa / immunology
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Respiratory Mucosa / metabolism
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Respiratory Mucosa / pathology
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STAT6 Transcription Factor / metabolism
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Th2 Cells / drug effects
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Allergens
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Hormones, Ectopic
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Intercellular Signaling Peptides and Proteins
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Interleukin-13
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Retnlb protein, mouse
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Interleukin-4
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Collagen