Basic and Clinical ImmunologyUpregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma☆,☆☆
Section snippets
Generation of the IL-13 proteins
IL-13 cDNA was cloned from a human TH2 cell clone, SM4.6.37 Because the cloned IL-13 was the R110 type, to replace an arginine residue with a glutamine residue, we used a PCR method with the primer 5′-GCGAGGGACAGTTCAACTGAAACTTC-3′ and its complement. Two types of the IL13 gene were incorporated into pMAL-cX vector (New England Biolabs, Beverly, Mass), with a TEV protease cleavage site (Gln-Asn-Leu-Tyr-Phe-Gln-Gly) attached to the N terminus of IL13 . As a result, the N terminus of the cleaved
Binding activity of the IL-13 variant with IL-13R α1
It has been already demonstrated that IL-13R consisting of IL-13Rα1 and IL-4Rα forms a high-affinity receptor with IL-13 and is capable of transducing the IL-13 signal, including STAT6 activation.28, 29, 30, 31, 32, 33 To address whether the binding activities of R110 and Q110 are different, we first used a human B-cell line, DND-39, transfected with IL-13Rα1. Scatchard analysis showed that this cell line expressed high- and low-affinity receptors, which are composed of IL-13Rα1 and IL-4Rα, and
Discussion
Many attempts have been made to elucidate genetic factors associated with bronchial asthma, with many genes being selected by using positional cloning and candidate gene approaches.3, 42 However, very few genes are reported to be functionally correlated with the pathogenesis of bronchial asthma. It is of great importance to investigate the functional differences of variants that correlated with the disease to exclude the possibility that any other polymorphisms in linkage disequilibrium evoke a
Acknowledgements
We thank Drs Dovie R. Wylie and Sho Matsushita for critical review of this manuscript and for providing a human TH2 clone, SM4.6, respectively. We also thank Drs Rie Sugimoto, Yoshito Abe, and Tomohiro Hamasaki for giving special technical comments.
References (49)
- et al.
The genetics and complexity of allergy and asthma
Immunol Today
(1998) - et al.
Recent advances in the genetics of allergy and asthma
Mol Med Today
(1999) - et al.
Genetics of asthma and inflammation: the status
Curr Opin Immunol
(1999) - et al.
Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families
Genomics
(2000) - et al.
Atopy and asthma: genetic variants of IL-4 and IL-13 signalling
Immunol Today
(2000) - et al.
A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children
J Allergy Clin Immunol
(2000) - et al.
An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS- 90)
J Allergy Clin Immunol
(2000) IL-12/IL-13 axis in allergic asthma
J Allergy Clin Immunol
(2001)The role of lymphocytes in allergic disease
J Allergy Clin Immunol
(2000)- et al.
Activating and inhibitory signaling in mast cells: new opportunities for therapeutic intervention?
J Allergy Clin Immunol
(2000)
IL-13 in allergy: home at last
Curr Opin Immunol
cDNA cloning and characterization of the human interleukin 13 receptor α chain
J Biol Chem
Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor α chain
J Biol Chem
The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway
Blood
IL-4/IL-13 signaling beyond JAK/STAT
J Allergy Clin Immunol
Cytokine receptor signaling pathways
J Allergy Clin Immunol
Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells
Biochem Biophys Res Commun
The role of IL-13 and its receptor in allergy and inflammatory responses
J Allergy Clin Immunol
The chimeric receptor between interleukin-2 receptor β chain and interleukin-4 receptor transduces interleukin-2 signal
Biochem Biophys Res Commun
Regulation of interleukin-13 receptor constituents on mature human B lymphocytes
J Biol Chem
Conversion of interleukin-13 into a high affinity agonist by a single amino acid substitution
J Biol Chem
Expression, purification, and characterization of recombinant human interleukin-13 from NS-0 cells
Protein Expr Purif
A genome-wide search for asthma susceptibility loci in ethnically diverse populations
Nat Genet
Genome-wide search for asthma susceptibility loci in a founder population
Hum Mol Genet
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2016, Advances in Medical SciencesCitation Excerpt :Computer modeling of rs20541 variant has shown that this substitution affects the signal strength between interleukin 13 and its receptor [6]. Arima et al. have found, using animal model, that IL13 with Gln110 variant has higher activity and is present in blood for a longer time [20]. This was confirmed by Chen et al. [29], who performed the experiments on mouse cell line with stable expression of human IL13R, that had the ability to bind human IL13.
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Supported by a Research Grant for Immunology, Allergy and Organ Transplant from the Ministry of Health and Welfare of Japan; a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, Culture, and Technology of Japan; RIKEN; Astra Zeneca Asthma Research Foundation; Japan Research Foundation for Clinical Pharmacology; grant AI43663 from the National Institute of Allergy and Infectious Diseases; and grant RSG-01-241-01-LIB from the American Cancer Society.
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Reprint requests: Kenji Izuhara, MD, PhD, Department of Biochemistry, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501, Japan.