期刊论文详细信息
BMC Infectious Diseases
IFN- alpha blocks IL-17 production by peripheral blood mononuclear cells in patients with chronic active hepatitis B Infection
Pu Chen2  Peng Luo2  Jiangping Meng1  Fang Cui2 
[1] Department of Obstetrics and Gynecology, Assisited Reproductive Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, Yuzhong District, China
关键词: IL-10;    IL-17;    IFN-α;    Chronic hepatitis B infection;   
Others  :  1134812
DOI  :  10.1186/1471-2334-14-55
 received in 2013-06-21, accepted in 2014-01-30,  发布年份 2014
PDF
【 摘 要 】

Background

IFN-α has been used to treat patients with chronic active hepatitis B (CAHB). Recent studies have implicated the IL-23/Th-17 pathway in the pathogenesis of CAHB. In this study, we investigated whether IFN-α could affect this pathway.

Methods

Peripheral blood mononuclear cells (PBMCs) obtained from patients with active CAHB (n = 61) and controls (n = 32) were cultured with or without IFN-α, and the levels of IL-17 and IL-10 in the supernatants were determined by ELISA, while the frequency of IL-17-expressing cells was measured by FACS. Similar experiments were also conducted with isolated CD4+ T cells from controls. Furthermore, an experiment using an anti-IL-10 antibody was performed to examine the underlying mechanisms of action of IFN-α.

Results

Both the levels of IL-17 and the frequency of IL-17-expressing cells were significantly higher in the PBMCs from CAHB patients than in the controls. IFN-α significantly decreased IL-17 production and the frequency of IL-17-expressing cells in PBMCs from both patients and controls. On the other hand, IFN-α increased IL-10 production by PBMCs from patients and controls. Anti-IL-10 antibody was able to neutralize the inhibitory effect of IFN-α on IL-17 production by PBMCs.

Conclusions

In vitro experiments showed that IFN-α could inhibit IL-17 expression and increase IL-10 production by PBMCs and CD4+ T cells. The inhibitory role of IFN-α on IL-17 production was partly mediated by IL-10.

【 授权许可】

   
2014 Cui et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150306075116447.pdf 786KB PDF download
Figure 5. 79KB Image download
Figure 4. 48KB Image download
Figure 3. 47KB Image download
Figure 2. 99KB Image download
Figure 1. 51KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Calvaruso V, Craxi A: Fibrosis in chronic viral hepatitis. Best Pract Res Clin Gastroenterol 2011, 25:219-230.
  • [2]Di Bisceglie AM: Hepatitis B and hepatocellular carcinoma. Hepatology 2009, 49(5 Suppl.):S56-S60.
  • [3]Zhang JY, Zhang Z, Lin F, et al.: Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology 2010, 51:81-91.
  • [4]Ye Y, Xie X, Yu J, et al.: Involvement of Th17 and Th1 effector responses in patients with Hepatitis B. J Clin Immunol 2010, 30:546-555.
  • [5]Hirohata S, Shibuya H, Tejima S: Suppressive influences of IFN-αlpha on IL-17 expression in human CD4+ T cells. Clin Immunol 2010, 134:340-344.
  • [6]Aman MJ, Tretter T, Eisenbeis I, et al.: Interferon-alpha stimulates production of interleukin-10 in activated CD4 + T cells and monocytes. Blood 1996, 87:4731-4736.
  • [7]de Waal MR, Haanen J, Spits H, et al.: Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991, 174:915-924.
  • [8]Beissert S, Hosoi J, Grabbe S, Asahina A, Granstein RD: IL-10 inhibits tumor antigen presentation by epidermalantigen-presenting cells. J Immunol 1995, 154:1280-1286.
  • [9]Fitzgerald DC, Zhang GX, El-Behi M, et al.: Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 2007, 8:1372-1379.
  • [10]European Association for the Study of the Liver: EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009, 50:227-242.
  • [11]Asian-Pacific consensus statement on the management of chronic hepatitisB: a 2012 update Hepatol Int 2012, 6:531-56.
  • [12]Zhao L, Tang Y, You Z, et al.: Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression. PLoS One 2011, 6:e18909.
  • [13]Ge J, Wang K, Meng QH, et al.: Implication of Th17 and Th1 cells in patients with chronic active hepatitis B. J Clin Immunol 2010, 30:60-67.
  • [14]Wu W, Li J, Chen F, et al.: Circulating Th17 cells frequency is associated with the disease progression in HBV infected patients. J Gastroenterol Hepatol 2010, 25:750-757.
  • [15]Li J, Wu W, Peng G, et al.: HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients. Immunol Cell Biol 2010, 88:834-841.
  • [16]Korn T, Bettelli E, Oukka M, Kuchroo VK: IL-17 and Th17 Cells. Annu Rev Immunol 2009, 27:485-517.
  • [17]Meyer O, et al.: Interferons and autoimmune disorders. Joint Bone Spine 2009, 76:464-473.
  • [18]Finter NB, Chapman S, Dowd P, et al.: The use of interferon-alpha in virus infections. Drugs 1991, 42:749-765.
  • [19]Zhang X, Jin J, Tang Y, Speer D, Sujkowska D, Markovic-Plese S: IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation. J Immunol 2009, 182:3928-3936.
  • [20]Penton-Rol G, Cervantes-Llanos M, Cabrera-Gomez JA, et al.: Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells frommultiple sclerosis patients. Int Immunopharmacol 2008, 8:881-886.
  • [21]Kubota N, Ebihara T, Matsumoto M, et al.: IL-6 and IFN-αlpha from dsRNA-stimulated dendritic cells control expansion of regulatory T cells. Biochem Biophys Res Commun 2010, 391:1421-1426.
  • [22]Pirhonen J, Siren J, Julkunen I, Matikainen S: IFN-αlpha regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages. J Leukoc Biol 2007, 82:1185-1192.
  • [23]Diveu C, McGeachy MJ, Boniface K, et al.: IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol 2009, 182:5748-5756.
  文献评价指标  
  下载次数:14次 浏览次数:5次