Il-13 Receptor Alpha 2: a Regulator of Il-13 and Il-4 Signal Transduction in Primary Human Fibroblasts.
From: Brooke Laboratories, Division of Infection, Inflammation, and Repair, UK.
The Journal of allergy and clinical immunology
- Publish Date: Oct 2006
- ISSN: 0091-6749
- Volume: 118
- Issue: 4
- Pages: 858-65
- Medium: Print
- Language: English
- Citation (JAMA): Andrews Allison-Lynn, Nasir Tosia, Bucchieri Fabio, et al. Il-13 Receptor Alpha 2: a Regulator of Il-13 and Il-4 Signal Transduction in Primary Human Fibroblasts.. J. Allergy Clin. Immunol. Oct 2006;118:858-65
Abstract
BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their use of a common receptor complex comprising IL-13 receptor alpha 1 (IL-13Ralpha1) and IL-4 receptor alpha (IL-4Ralpha). The nonsignaling receptor IL-13 receptor alpha 2 (IL-13Ralpha2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13. OBJECTIVE: We sought to examine the inhibitory effects of soluble and membrane-bound IL-13Ralpha2 on IL-13- and IL-4-mediated effects. METHODS: Primary human fibroblasts were grown from endobronchial biopsy specimens obtained from volunteers. Upregulation of IL-13Ralpha2 mRNA was measured by means of RT-PCR, and the level of surface expression was measured by means of FACS. RESULTS: We found that a recombinant soluble form of IL-13Ralpha2 blocked the effects of IL-13, but not IL-4, in fibroblasts in vitro. However, we found that the transmembrane form of IL-13Ralpha2 could attenuate both IL-13 and IL-4 responses, even though the response to TNF-alpha was unaffected. Furthermore, we found that IL-13Ralpha2 became associated with IL-4Ralpha in the presence of IL-4. Addition of a blocking antibody to the extracellular domain of IL-13Ralpha2 restored responses of both IL-13 and IL-4. CONCLUSION: The ability of IL-13Ralpha2 to regulate IL-4 was previously unrecognized in primary airway cells. These data reveal a novel role for IL-13Ralpha2 as a negative regulator of both IL-13 and IL-4 signaling in human bronchial fibroblasts. CLINICAL IMPLICATIONS: It appears that IL-13Ralpha2 might be a powerful suppressor of TH2-mediated responses and thus represents a potential therapeutic target for the treatment of asthma.
Mesh Headings (Keywords): Bronchi, Cells, Cultured, Fibroblasts, Flow Cytometry, Gene Expression, Humans, Interleukin-13, Interleukin-4, RNA, Messenger, Receptors, Interleukin-13, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17030238
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