The Effects Of MiR-146a On The Regulation Of Inflammation And The Expression Level Of It In The Serum Of SLE Patients

Backgrounds: MiR-146 a is a kind of microRNA which is highly expressed in mononuclear cells and T cells and other immune cells.Recently,some studies revealed that there was downexpression of miR-146 a in peripheral blood mononuclear cell of systemic lupus eythematosus,suggesting miR-146 a might be associated with immunological reactions of systemic lupus eythematosus,but the specific mechanism of it is unclear now.IL-1 receptor-associated kinase l is one of the target of miR-146 a which also is the important molecule in cell signal transduction of inflammation.Toll like receptor 4 is a kind of receptors mediated the transmembrane signal transduction of natural immune response,through activating the nuclear factor-?B start the inflammatory response.Therefore,this study firstly observed whether the miR-146 a participates in the regulation of the inflammatory response through regulating IRAK1.Although there is evidence that miR-146 a is abnormal expressed in somatic cell of SLE patients,but its level of expression in serum and its clinical significance is not clear,so this study also explore the expression level of miR-146 a in the serum of SLE patients and its clinical significance.Objectives: The present study was aimed to investigate whether miR-146 a regulate the signal path of TLR4/NF-?B involved in the regulation of inflammation through its target gene interleukin-1 receptor-associated kinase l.Simultaneously,this study discussed the expression level of miR-146 a in serum of SLE patients and its clinical significance.Methods: The present study raised and lowered the expression level of miR-146 a in human acute monocytic leukemia cells by transfected miR-146 a mimic and miR-146 a inhibitor,to observe the effects of miR-146 a on the expression of IRAK1.On this basis,we excited the cell inflammation through the use of LPS stimulated THP-1cells,then detected the level of NF-?B in the nuclear and the level of IL-6 and TNF-?in cell culture supernatant,to observe the role of miR-146 a in the activation of NF-?B and the secretion of proinflammatory cytokines.Collecting 120 cases of hospitalized patients with SLE and 30 cases of healthy physical examination,by detecting thelevel of miR-146 a,IL-6 and TNF-? in serum,to analysis the clinical significance of serum miR-146 a in SLE patients.Results: MiR-146 a significantly reduced the expression of IRAK1 in the THP-1 cells,reduced the level of NF-?B in the nucleus and the level of IL-6 and TNF-? in cell culture supernatant,compared with the corresponding control group(P<0.01).The level of serum miR-146 a in SLE patients significantly lower than the healthy control group,P<0.01;Compared with inactive groups,the expression level of serum miR-146 a in the activity groups was decreased,but no statistical difference(P>0.05).Serum miR-146 a as a clinical laboratory markers,its sensitivity was 80.0%,specificity was 75.0%,had certain diagnostic value for SLE.Analyzed the correlation of proinflammatory cytokines and serum miR-146 a which was from the 10 cases of healthy volunteers and 30 cases of SLE patients,we found that the delta CT value of miR-146 a was positively correlated with the level of TNF-?,correlation coefficient r= 0.478,P < 0.01,but no obvious correlation with the levels of IL-6(P>0.05).Conclusion:(1)The miR-146 a inhibited the expression of its target gene of IRAK1 mRNA and protein,when the expression of miR-146 a was inhibited,the IRAK1 mRNA and protein expressed increased,it showed that the miR-146 a has a role to negative regulation of IRAK1.(2)After overexpressing the miR-146 a,NF-?B protein decreased significantly,the levels of IL-6,TNF-? in the cell supernatant were reduced significantly,after inhibiting the miR-146 a,NF-?B protein increased significantly,the levels of IL-6,TNF-? in the cell supernatant were increased significantly.It showed that miR-146 a can through regulating the target gene IRAK1 to regulat the signaling pathway of NF-?B/TLR4,influencing the secretion of inflammatory cytokines.(3)The miR-146 a in SLE patients with significantly lower levels,as a clinical laboratory marker,its sensitivity was 80%,specificity was 75%,it might be became a new clinical laboratory markers.(4)The levels of IL-6 and TNF-? in the serum of SLE patients were significantly increased,which had great significance to the development of SLE disease.(5)The relative expression level of miR-146 a has significant negatively correlation with the levels of TNF-?.SLE disease may had abnormal expression of miR-146 a which through its target gene IRAK1 negative regulationTLR/NF-kB signal pathway,promoting the downstream inflammatory cytokine IL-6and TNF-? secretion,so to affect the occurrence and development of the disease.