miR-33s Negatively Regulates LPS-induced Production of Inflammatory Cytokines by Targeting p38 MAPK_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhaoZhenyu ,  WangDeming , XiaoJi

Department of Anesthesiology, The Second Affiliated Hospital of Nanhua University, Hengyang, Hunan, 421001, China;

Corresponding author：

WangDeming, Email: 958467329@qq.com

Keywords：

Lipopolysaccharide; micro RNA; p38 mAPK; Inflammatory factor; Monocytes

DOI：

10.7507/1671-6205.2015040

Video：

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Objective To investigate whether the miR-33s negatively regulates LPS-induced production of inflammatory cytokines by targeting p38 MAPK. Methods Human monocytes THP-1 cells were cultured in vitro and transfected with miR-33s mimic (25 nmol/L) or miR-33s inhibitor (25 nmol/L)by TransIT-X2^® Dynamic Delivery System for 24 h. Then the transfected THP-1 cells were stimulated by LPS of 10.0 ng/mL for 24 h. The expression of miR-33s and p38 MAPK protein were measured by semi-quantitative RT-PCR. The concentrations of TNF-α,IL-6 and IL-1β in the cultured supernatant were assessed by ELISA. Results The transfection of miR-33s mimic significantly increased the release of TNF-α,IL-6 and IL-1β(P<0.05). The expression of p38 MAPK protein was also significantly reduced(P<0.05). However,the pre-treatment of miR-33s inhibitor reversed the LPS-induced release of TNF-α,IL-6,and IL-1β,and the expression of p38 MAPK protein of THP-1 cells. Conclusion miR-33s may play an important role in the regulation in inflammatory factors released from THP-1 cells by targeting p38 MAPK.

Citation： ZhaoZhenyu, WangDeming, XiaoJi. miR-33s Negatively Regulates LPS-induced Production of Inflammatory Cytokines by Targeting p38 MAPK. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(2): 157-160. doi: 10.7507/1671-6205.2015040 Copy

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1. Ambros V.The functions of animal microRNAs.Nature,2004,431:350-355.
2. Bartel DP.MicroRNAs:target recognition and regulatory functions.Cell,2009,136:215-233.
3. Jing Q, Huang S, Guth S,et al.Involvement of microRNA in AU-rich element-mediated mRNA instability.Cell,2005,120:623-634.
4. Rayner KJ,Suárez Y,Dávalos A,et al.MiR-33 contributes to the regulation of cholesterol homeostasis.Science,2010,328:1570-1573.
5. Najafi-Shoushtari SH, Kristo F, Li Y, et al.MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis.Science,2010,328:1566-1569.
6. Gazzar ME, Mccall CE.MicroRNAs distinguish translational from transcriptional silencing during endotoxin tolerance.J Biol Chem,2010,285:20940-20951.
7. Levy MM, Fink MP, Marshall JC, et al.2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference.Intensive Care Med,2003,29:530-538.
8. Leder JA,Rodrick ML,Mannick JA.The effects of injury on the adaptive immuneresponse.Shock,1999,11:153-159.
9. Takashi M,Ryoske T,Motoki F,et al.Serum macrophge migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients:an observational study.BMC Infect Dis,2009,12:209-219.
10. Ding Y,Boguslawski EA,Berghuis BD,et al.Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma.Mol Cancer Ther,2008,7:648-658.
11. Shin BA, Yoo HG, Kim HS,et al.p38 MAPK pathway is involved in the urokinase plasminogen activator expression in humang astric SNU-638 cells.Oncol Rep,2003,10:1467-1471.
12. O'Connell RM, Rao DS, Chaudhuri AA, et al. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol, 2010,10:111-122.
13. Tili E,Michaille JJ,Cimino A, et al.Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock.J Immunol,2007,179:5082-5089.
14. Ho PC,Chang KC,Chuang YS,et al.Cholesterol regulation of receptor-interacting protein 140 via microRNA-33 in inflammatory cytokine production.FASEB J,2011,25:1758-1766.
15. Fritah A,Christian M, Parker MG.The metabolic coregulator RIP140:an update.Am J Physiol Endocrinol Metab,2010,299:E335-E340.
16. Marquart TJ, Allen RM,Ory DS,et al.miR-33 links SREBP-2 induction to repression of sterol transporters.Proc Natl Acad Sci USA,2010,107:12228-12232.

Chinese Journal of Respiratory and Critical Care Medicine

miR-33s Negatively Regulates LPS-induced Production of Inflammatory Cytokines by Targeting p38 MAPK

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