A Study About The Effect Of HuR On Pro-inflammatory Gene Expression In Acute Mice Lung Inflammation

Inflammation plays critical roles in host defenses and damage repair, its not only preserveing the normal state of organism,but also the incentives of many inflammation related disease. Cytokines and chemokines are critical mediators of inflammation and host defenses. Regulation of cytokines and chemokines as the central part in inflammation can occur at various stages of gene expression, including transcription, mRNA export, and post-transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines and chemokines by modulating mRNA stability.Regulation of the stability of mRNA are mainly controled by RNA binding proteins (RBPs) and microRNAs. A large number of RNA binding proteins and microRNAs target mRNA's AU-rich elements (AREs) located in 3'untranslated region (3'UTR), thereby affecting the target mRNA's stability and translation. As a ubiquitously expressed mRNA binding protein, The roles of HuR related to the fate of mRNA in cytoplasm has been widely studied. HuR affectes its target mRNAs(for instance cytokines TNF-a and chemokines Cxcl-2 mRNA) stability by binding with the AREs in mRNA's 3'UTR. Regulation of the stability about these chemokines and cytokines' mRNA can significantly influence the procession of inflammation and related diseases. The effect of HuR on target mRNA determined by the identification and binding between the RNA recognition domain located in HuR structure and RNA specificc sequence contained in the structure of the target mRNAs. Under different physiological and pathological conditions, The function of HuR are different due to different modifications on HuR. The function of HuR is affected by different post -translational modifications in specific reactions.PARP-1, a widely studied ribozyme,is known as its important effects in DNA damage and gene expression regulation-mnaily on transcriptional level.The function of PARP-1 also related to many diseases, specifically in inflammation, but the function of PARP-1 in post-transcriptional regulation is still unknow.In this study, using LPS-induced acute mice lung inflammation model, we detected TNF-a, Cxcl-2 mRNA and PARlytion of HuR and whole proteins under different conditions (whether there is PARP-1 inhibitor PJ34 intervention) of mouse lung tissue. The results revealed that PARP-1 inhibitor PJ34 can significantly inhibit LPS-induced inflammation in mice lung, The activation of PARP-1 and the PARylation are suppressed. The binding of HuR and it target gene cxcl-2 mRNA also influenced by the suppression of PARP-1's activition. The results suggest that,in acute lung inflammation, PARP-1 involved in the regulation of pro-inflammatory gene cxcl-2 mRNA stability by PARylate HuR, which is a proof of PARP-1 as a regulator that can regulate HuR's function through Parylate HuR.