The Expression And Significance Of TRAF Etc In Condyloma Acuminatum Caused By Low Risk HPV

Background and ObjectiveThe major clinical manifestations of Condyloma acuminatum(CA)is very common and associated with benign and malignant epithelial proliferations of skin and internal squamous mucosae.The incidence of Condyloma acuminatum is rising year by year.The disease has become one of the most common Sexually Transmitted Disease(STD)in our country.The human papilloma virus(HPV)is pathogens of Condyloma acuminatum.HPV is a tiny DNA viruses of Papivaviridae.HPV has not success culture in vitro because only host of HPV is the complex layer squamous epithelium of human skin and mucous membrane.According to the irulence,HPV divided into high-risk type and low-risk type.High-risk type including 16,18,etc;low-risk type has 6,11,etc.The HPV subtypes of Condyloma acuminatum including:HPV 6,11,16,18,30,42,43,44,45,51,54,55,70.Generally speaking,the occurrence of Condyloma acuminatum depends on the number of HPV pathogens infection and the body's immune status.The body's immune generally divided into natural immune and acquired immune.In a way,natural immune is more important.Natural immune can affect many respects of acquired immune function through induce more inflammation factors and cytokines released,.Toll-like receptors(TLRs)is widely distributed in the surface of immune cells.They can play a important role through recognition and combining PAMPs(Pathogen associated molecular pattern)because themselves are a kind of pattern recognition receptors.Therefore,TLRs can be widely identification pathogenic microbes,activate the natural immune cell and coupling signaling pathways,lead to more range of a series of immune response.Myeloid differentiation factor 88(MyD88),IL-1/Toll-like receptor associated kines 1(IRAK1),Tumor necrosis factor receptor associated factor 2(TRAF2),Tumor necrosis factor receptor associated factor 6(TRAF6),TGF-beta activated kinase 1(TAK1)and Apoptosis signal-regulating kinase 1(ASK1)are critical molecules of Toll-like receptors(TLRs)related signal transmission processMyD 8 8 has TIR structure domain and death structure domain(DD).MyD8 8 is a key joint molecules of TLRs signal pathway.MyD88 played an important role in transfer information and the process of disease development.MyD88 have particular concern with some disease,such as immune tolerance,inflammatory bowel disease,cardiovascular disease.IRAK is a serine/threonine specific kinase.The human body has been found at least four IRAK:IRAK1,IRAK2,IRAK3(M)and IRAK4.IRAK1 plays an important role in regulation of the natural immunity.IRAK1 and IRAK4 have the kinase activity.IRAK1 and IRAK4 have Closely linked to each other.Almost all of the TLRs related to signal transduction receptor in connection with them.MyD88 and TRAF6 Toll are critical molecules of TLRs related signal transmission process and their signal transduction each other must be mediated by IRAK1.TNF receptor associated factors(TRAFs)is a kind of important adjustment factor of physiological and pathological process.TRAFs play an important role in natural immune and acquired immune.TRAFs is as an critical component of IL-1R/TLR superfamily signaling pathways.In the B lymphocytes of human body,TRAF2 can competite with TRAF6 and reduce the ability of CD40 triggered the nf-kappa B signaling pathways.ASK1 distributed widely in the body.The ASK1 could participate in many cell function activities and pathological process.ASK1 plays an important role in apoptosis mediated by tumor necrosis factor a(TNF alpha).In TRAF protein family,TRAF1/2/3/5/6 are interaction with ASK1,and TRAF2/5/6 increased activity of ASK1.ASK1 can be activated by excessive expression of TRAF2 and TRAF6.At present,the treatment of condyloma acuminatum were no satisfaction treatment method and has not found the method of eradicated HPV completely.The treatment cannot be fundamentally solved the problem of recurrence now.Many reports in the literature proved that immune therapy have good effect.This experiment concern of low risk human papilloma virus(HPV6,11),studying on the expressions of six genes between condyloma acuminatum group and the normal control group and the immune mechanism of condyloma acuminatum.MethodsWe use of 21 types of human papilloma virus of nucleic acid amplification reagents,screening low risk human papilloma virus(HPV6,11)from clinical collection of 30 patients condyloma acuminatum specimens,13 cases of normal adult foreskin as normal control group.Trizol methods to extract organization total RNA,reverse transcription to cDNA,applicate real-time quantitative fluorescence PCR,SYBR Green dye detection method.Housekeeper gene ?-actin as the reference gene.After ensure ?-actin were constant expression in the two groups and then detect the expression of MyD88,IRAK1,TRAF2,TRAF6,TAK1,ASK1.Statistical processing use2-??Ct and Independent sample T Test,?=0.05.ResultsIn the 30 cases of condyloma acuminatum specimens,HPV 6 infections only found in 3 cases(10.0%,3/30 cases),HPV 11 only has 8 cases(26.7%,8/30 cases),HPV 6 and 11 were 13 cases'(43.3%,13/30 cases),HPV(18,33,52,53 and 68)6 cases(20.0%,6/30).Low risk human papilloma virus(HPV6,11)infected 24 cases and Infection rates was 80%.In the two groups,the expression of ?-actin relatively constant.2-??Ct method is used to calculate the each sample 2-??Ct result.With the Independent sample T Test found that:TAK1 difference was no significant(P>0.05);MyD88,IRAK1,TRAF2,TRAF6,ASK 1 have the statistical significance(P<0.05).ConclusionsFrom condyloma acuminatum clinical specimens,HPV infection rate was 100%.The infection rate of HPV6/11 were 80%,the low risk type HPV6/11 are the main types of condyloma acuminatum.According to the real-time quantitative fluorescence PCR shows that MyD8 8,IRAKI,TRAF2,TRAF6,ASK1 were over active in condyloma acuminatum group and the TAK1 was no change between two groups.The differences of expressions of MyD88,IRAK1,TRAF2,TRAF6,ASK1 indicated that TLRs mediated pathways plays an important role in the immune mechanism of condyloma acuminatum.