Expression of CD39 mRNA is altered in the peripheral blood of patients with allergic asthma

Wang,Lin‑Lin; Tang,Ping‑Hua; Shi,Chao‑Guo; Wan,Ying‑Huan; Tang,Wei; Hou,Xia‑Xiao; Pan,Na‑Li; Shi,Yu‑Bao; Tao,Qin‑Lian

doi:10.3892/br.2013.196

Expression of CD39 mRNA is altered in the peripheral blood of patients with allergic asthma

Authors:
- Lin‑Lin Wang
- Ping‑Hua Tang
- Chao‑Guo Shi
- Ying‑Huan Wan
- Wei Tang
- Xia‑Xiao Hou
- Na‑Li Pan
- Yu‑Bao Shi
- Qin‑Lian Tao
View Affiliations

Affiliations: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China, Department of Pulmonary Medicine, Qingdao Municipal Hospital, Qingdao University School of Medicine, Qingdao, Shandong 266011, P.R. China
Published online on: November 6, 2013 https://doi.org/10.3892/br.2013.196
Pages: 75-78

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The ectoenzyme CD39 hydrolyzes extracellular adenosine 5'-triphosphate (ATP), which possesses pro‑inflammatory properties. However, the role of CD39 in allergic asthma has not been fully elucidated. A total of 18 patients with persistent asthma who were allergic to house dust mites and 19 healthy volunteers were enrolled in this study. The expression of CD39, GATA3, RAR-related orphan receptor γ (ROR‑γt) and forkhead box P3 (Foxp3) mRNA in peripheral blood mononuclear cells (PBMCs) was determined by SYBR‑Green I quantitative polymerase chain reaction (qPCR). The cytokines interleukin (IL)‑4, IL‑17A, transforming growth factor β (TGF‑β) and DP.sIgE were detected by enzyme-linked immunosorbent assay. Our data demonstrated that the expression of CD39 mRNA in PBMCs from asthmatic patients was significantly lower compared to that in normal controls [(1.49±0.59)x10‑3 vs. (2.17±0.77)x10‑3, respectively; P<0.01]. CD39 mRNA was negatively correlated with serum IL‑4, IL‑17A and GATA3 expression (r=‑0.468, P<0.05; r=‑0.550, P<0.05; and r=‑0.424, P<0.01, respectively) and positively correlated with Foxp3 and TGF‑β expression (r=0.373, P<0.05; and r=0.425, P<0.05, respectively). There was no obvious correlation between CD39 and ROR‑γt expression (r=‑0.259, P=0.122). These data suggested that CD39 mRNA expression was downregulated in allergic asthma, which was positively correlated with serum IL‑4, IL‑17A and GATA3 expression and negatively correlated with serum TGF‑β and Foxp3 expression, whereas there was no correlation with ROR‑γt. Therefore, it was hypothesized that CD39 may participate in the occurrence and progression of allergic asthma.

View Figures

View References

1	Maliszewski CR, Delespesse GJ, Schoenborn MA, et al: The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization. J Immunol. 153:3574–3583. 1994.PubMed/NCBI
2	Koziak E, Sevigny J, Robson SC, Siegel JB and Kaczmarek K: Analysis of CD39/ATP diphosphohydrolase (ATPDase) expression in endothelial cells, platelets and leukocytes. Thromb Haemost. 82:1538–1544. 1999.PubMed/NCBI
3	Day YJ, Huang L, Ye H, Li L, Linden J and Okusa MD: Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4⁺T cells and IFN-gamma. J Immunol. 176:3108–3114. 2006. View Article : Google Scholar : PubMed/NCBI
4	Ohta A and Sitkovsky M: Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 414:916–920. 2001. View Article : Google Scholar : PubMed/NCBI
5	Erdmann AA, Gao ZG, Jung U, Foley J, Borenstein T, Jacobson KA and Fowler DH: Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo. Blood. 105:4707–4714. 2005. View Article : Google Scholar : PubMed/NCBI
6	Sipka S, Kovacs I, Szanto S, Szegedi G, Brugos L, Bruckner G and Jozsef Szentmiklosi A: Adenosine inhibits the release of interleukin-1beta in activated human peripheral mononuclear cells. Cytokine. 31:258–263. 2005. View Article : Google Scholar : PubMed/NCBI
7	Lappas CM, Rieger JM and Linden J: A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4⁺T cells. J Immunol. 174:1073–1080. 2005. View Article : Google Scholar : PubMed/NCBI
8	Imai M, Goepfert C, Kaczmarek E and Robson SC: CD39 modulates IL-1 release from activated endothelial cells. Biochem Biophys Res Commun. 270:272–278. 2000. View Article : Google Scholar : PubMed/NCBI
9	Warny M, Aboudola S, Robson SC, Sevigny J, Communi D, Soltoff SP and Kelly CP: P2Y₆nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide. J Biol Chem. 276:26051–26056. 2001.
10	la Sala A, Ferrari D, Corinti S, Cavani A, Di Virgilio F and Girolomoni G: Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses. J Immunol. 166:1611–1617. 2001.PubMed/NCBI
11	Deaglio S, Dwyer KM, Gao W, et al: Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 204:1257–1265. 2007. View Article : Google Scholar : PubMed/NCBI
12	Huang S, Apasov S, Koshiba M and Sitkovsky M: Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood. 90:1600–1610. 1997.PubMed/NCBI
13	Zhou L, Chong MM and Littman DR: Plasticity of CD4⁺T cell lineage differentiation. Immunity. 30:646–655. 2009.
14	Dong C: TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 8:337–348. 2008. View Article : Google Scholar : PubMed/NCBI
15	Shi YH, Shi GC, Wan HY, et al: Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. Chin Med J (Engl). 124:1951–1956. 2011.PubMed/NCBI
16	Shi YH, Shi GC, Ma JY, AI XY, Zhu HX and Wan HY: Expression of T-bet, GATA-3, RORγt and Foxp3 mRNA in the peripheral blood of allergic asthma. Journal of Internal Medicine Concepts and Practice. 6:113–116. 2011.(In Chinese).
17	Weaver CT, Harrington LE, Mangan PR, Gavrieli M and Murphy KM: Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 24:677–688. 2006. View Article : Google Scholar : PubMed/NCBI
18	Zhu J, Yamane H, Cote-Sierra J, Guo L and Paul WE: GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 16:3–10. 2006. View Article : Google Scholar
19	Chen Q, Yang W, Gupta S, et al: IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity. 29:899–911. 2008. View Article : Google Scholar : PubMed/NCBI
20	Ivanov II, McKenzie BS, Zhou L, et al: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17⁺T helper cells. Cell. 126:1121–1133. 2006. View Article : Google Scholar : PubMed/NCBI
21	Tesmer LA, Lundy SK, Sarkar S and Fox DA: Th17 cells in human disease. Immunol Rev. 223:87–113. 2008. View Article : Google Scholar : PubMed/NCBI
22	Josefowicz SZ and Rudensky A: Control of regulatory T cell lineage commitment and maintenance. Immunity. 30:616–625. 2009. View Article : Google Scholar : PubMed/NCBI
23	Zhao J, Lloyd CM and Noble A: Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling. Mucosal Immunol. 6:335–346. 2013. View Article : Google Scholar : PubMed/NCBI
24	Shevach EM: CD4⁺CD25⁺suppressor T cells: more questions than answers. Nat Rev Immunol. 2:389–400. 2002.
25	Erpenbeck VJ, Hagenberg A, Krentel H, et al: Regulation of GATA3, c-maf and T-bet mRNA expression in bronchoalveolar lavage cells and bronchial biopsies after segmental allergen challenge. Int Arch Allergy Immunol. 139:306–316. 2006. View Article : Google Scholar : PubMed/NCBI
26	Curotto de Lafaille MA, Kutchukhidze N, Shen S, et al: Adaptive Foxp3⁺regulatory T cell-dependent and -independent control of allergic inflammation. Immunity. 29:114–126. 2008.
27	Borsellino G, Kleinewietfeld M, Di Mitri D, et al: Expression of ectonucleotidase CD39 by Foxp3⁺Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 110:1225–1232. 2007. View Article : Google Scholar : PubMed/NCBI
28	Fletcher JM, Lonergan R, Costelloe L, et al: CD39⁺Foxp3⁺regulatory T cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol. 183:7602–7610. 2009.PubMed/NCBI
29	Ohta A, Kini R, Ohta A, Subramanian M, Madasu M and Sitkovsky M: The development and immunosuppressive functions of CD4⁺CD25⁺FoxP3⁺regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol. 3:1902012.
30	Michel ML, Pang DJ, Haque SF, Potocnik AJ, Pennington DJ and Hayday AC: Interleukin 7 (IL-7) selectively promotes mouse and human IL-17-producing γδ cells. Proc Natl Acad Sci USA. 109:17549–17554. 2012.PubMed/NCBI