Lnc-DC regulates cellular turnover and the HBV-induced immune response by TLR9/ STAT3 signaling in dendritic cells

• Autorzy: Zhuang L. , Tian J. , Zhang X. , Wang H. , Chuang C.
• Języki publikacji: EN

Abstrakty

EN

Background: Lnc-DC is a specific group of long non-coding (Lnc) RNAs in dendritic cells (DCs). Its function has been previously studied, and includes roles in dendritic cell differentiation and the progression of some diseases. In this study, we observed the critical role of Lnc-DC in regulating the differentiation, growth, and apoptosis of dendritic cells. Methods: We first isolated peripheral blood mononuclear cells to culture and induce into DCs, which were then co-cultured with hepatitis B virus (HBV)-secreting HepG2. 2.15 cells for the detection of changes in Lnc-DC. The expression levels of TLR9, p-STAT3, and SOCS3 were tested with qPCR and western blot. MTT assays were used to analyze the cell proliferation, cell cycle, and apoptosis. We used ELISA to test the expression of TNF-α, IL-1β, IL-6, IL-12p40, and IFN-γ. Results: Co-culture with HBV-secreting HepG2.2.15 cells increased the level of Lnc-DC and activated TLR9/STAT3 signaling. The HBV DNA level (IU/ml) was positively correlated with levels of Lnc-DC and TLR9, further demonstrating that Lnc-DC was associated with the immune response of HBV. Lnc-DC was shown to regulate TLR9/ STAT3 signaling in dendritic cells. More interestingly, the regulation of Lnc-DC controlled the immune response by reducing the concentration of secreted TNF-α, IL-6, IL-12, and IFN-γ, as well as increasing the IL-1β concentration in dendritic cells. Conclusion: Lnc-DC is important in regulating the growth, apoptosis, and immune response of dendritic cells mediated by TLR9/STAT3 signaling, and was also activated by HBV. This study provides a previously unidentified mechanism underlying the immune response in dendritic cells.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2018
• Tom: 23
• Opis fizyczny: p.1-9,fig.,ref.

Twórcy

autor

Zhuang L.

• Department of Infectious Disease, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, Shenzhen 518101, China

autor

Tian J.

• Department of Infectious Disease, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, Shenzhen 518101, China

autor

Zhang X.

• Department of Infectious Disease, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, Shenzhen 518101, China

autor

Wang H.

• Department of Infectious Disease, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, Shenzhen 518101, China

autor

Chuang C.

• Department of Infectious Disease, the Affiliated Shenzhen Baoan Hospital of Southern Medical University, Shenzhen 518101, China
• Department of Infectious Disease, Shenzhen Baoan District People’s Hospital, No. 118, Xin’an Street, Long Jing er Raod, Shenzhen 518101, China

Bibliografia

• 1. Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q, Cao X. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014;344:310–3.
• 2. Alikhah A, Pahlevan Kakhki M, Ahmadi A, Dehghanzad R, Boroumand MA, Behmanesh M. The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus. J Diabetes Complicat. 2018;32:258–65.
• 3. Wu GC, Li J, Leng RX, Li XP, Li XM, Wang DG, Pan HF, Ye DQ. Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus. Oncotarget. 2017;8:23650–63.
• 4. Zhang W, Zhou Y, Ding Y. Lnc-DC mediates the over-maturation of decidual dendritic cells and induces the increase in Th1 cells in preeclampsia. Am J Reprod Immunol. 2017;77.
• 5. Wen Z, Zhong Z, Darnell JE Jr. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995;82:241–50.
• 6. Hossain DM, Pal SK, Moreira D, Duttagupta P, Zhang Q, Won H, Jones J, D'Apuzzo M, Forman S, Kortylewski M. TLR9-targeted STAT3 silencing abrogates immunosuppressive activity of myeloid-derived suppressor cells from prostate Cancer patients. Clin Cancer Res. 2015;21:3771–82.
• 7. Moreira D, Zhang Q, Hossain DM, Nechaev S, Li H, Kowolik CM, D'Apuzzo M, Forman S, Jones J, Pal SK, Kortylewski M. TLR9 signaling through NF-kappaB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells. Oncotarget. 2015;6:17302–13.
• 8. Hsu K, Chung YM, Endoh Y, Geczy CL. TLR9 ligands induce S100A8 in macrophages via a STAT3-dependent pathway which requires IL-10 and PGE2. PLoS One. 2014;9:e103629.
• 9. Emi N, Kanzaki H, Yoshida M, Takakura K, Kariya M, Okamoto N, Imai K, Mori T. Lymphocytes stimulate progesterone production by cultured human granulosa luteal cells. Am J Obstet Gynecol. 1991;165:1469–74.
• 10. Hashii K, Fujiwara H, Yoshioka S, Kataoka N, Yamada S, Hirano T, Mori T, Fujii S, Maeda M. Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation. Hum Reprod. 1998;13:2738–44.
• 11. Sun D, Nassal M. Stable HepG2- and Huh7-based human hepatoma cell lines for efficient regulated expression of infectious hepatitis B virus. J Hepatol. 2006;45:636–45.
• 12. Gehring AJ, Ann D'Angelo J. Dissecting the dendritic cell controversy in chronic hepatitis B virus infection. Cell Mol Immunol. 2015;12:283–91.
• 13. Marhaba R, Nazarenko I, Knöfler D, Reich E, Voronov E, Vitacolonna M, Hildebrand D, Elter E, Apte RN, Zöller M. Opposing effects of fibrosarcoma cell-derived IL-1 alpha and IL-1 beta on immune response induction. Int J Cancer. 2008;123:134.
• 14. Keswani T, Sarkar S, Sengupta A, Bhattacharyya A. Role of TGF-β and IL-6 in dendritic cells, Treg and Th17 mediated immune response during experimental cerebral malaria. Cytokine. 2016;88:154–66.
• 15. Zhang Z, Chen D, Yao J, Zhang H, Jin L, Shi M, Zhang H, Wang FS. Increased infiltration of intrahepatic DC subsets closely correlate with viral control and liver injury in immune active pediatric patients with chronic hepatitis B. Clin Immunol. 2007;122:173–80.
• 16. Beckebaum S, Cicinnati VR, Dworacki G, Muller-Berghaus J, Stolz D, Harnaha J, Whiteside TL, Thomson AW, Lu L, Fung JJ, Bonham CA. Reduction in the circulating pDC1/pDC2 ratio and impaired function of ex vivo-generated DC1 in chronic hepatitis B infection. Clin Immunol. 2002;104:138–50.
• 17. Tavakoli S, Schwerin W, Rohwer A, Hoffmann S, Weyer S, Weth R, Meisel H, Diepolder H, Geissler M, Galle PR, et al. Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection. J Gen Virol. 2004;85: 2829–36.
• 18. Xue J, Liao L, Yin F, Kuang H, Zhou X, Wang Y. LncRNA AB073614 induces epithelial- mesenchymal transition of colorectal cancer cells via regulating the JAK/STAT3 pathway. Cancer Biomark. 2018;21:1-10.
• 19. Chen JF, Wu P, Xia R, Yang J, Huo XY, Gu DY, Tang CJ, De W, Yang F. STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy. Mol Cancer. 2018;17:6.
• 20. Li S, Mei Z, Hu HB. The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis. J Cell Physiol. 2018;233(9):6679–88.
• 21. Liu BS, Cao Y, Huizinga TW, Hafler DA, Toes RE. TLR-mediated STAT3 and ERK activation controls IL-10 secretion by human B cells. Eur J Immunol. 2014;44:2121–9.

Identyfikatory

DOI

10.1186/s11658-018-0108-y