Effect Of Lipoxin A4in NF-κBp65Signaling Pathway Of Oral Lichen Planus

ObjectiveTo observe the expression of lipoxin A4receptor (ALX-R) and nuclearfactor-kappa Bp65(NF-κBp65) protein in both oral lichen planus lesions(OLP) andnormal oral mucosa（NOM）tissues, as well as to analyse the influence of differentconcentrations of15-epi-LXA4, which is LXA4analogs, on OLP inflammationHaCaT cell model, which was induced by lipopolysaccharide(LPS), to discuss thefunction of LXA4on oral lichen planus pathogenesis.MethodsPart I：(1) HE staining method was used to observe OLP and NOM tissue toselected the qualified specimens.(2)Immunohistochemical staining was used to detectthe expression of LXA4receptor (ALX-R) and NF-κBp65protein in OLP and NOMtissue,then compare and analyse correlation and deviation of two indicators.Part II：(1) In order to mimic the local OLP immune environment to some extent,HaCaT(keratinocytes) were stimulated with LPS; ELISA method was used to observethe IL-6expression in HaCaT that were intervened by10g/mL LPS with differenttime:6、12、24h;(2) Different concentrations of15-epi-LXA4were added in HaCaTmedium to stimulate the OLP inflammatory model, and culture supernatants and totalcell RNA were obtained at6,12,24hours respectively; detect and analyse the effectsof different15-epi-LXA4concentrations on the expression of IL-6and NF-κBp65mRNAin OLP cell model.ResultsPart I：(1) The positive expression rate of ALX-R protein was downregulated inOLP(43.3%) compared to normal oral mucosa(90%),(P<0.05),(2) The positiveexpression rate of NF-Bp65protein was upregulated in OLP (83.3%) compared to normal oral mucosa(20%),(P<0.01) and NF-Bp65expression in erosive type aresignificantly higher than reticulate type (P<0.05);(3)NF-κBp65and ALX-R arenegatively related, both in OLP and NOM.Part II：(1) In the OLP inflammation cell model we built, the expression ofinflammatory factor IL-6protein increased obviously, in coordinate with time;（2）Certain concentrain of15-epi-LXA4can inhibit the expression of NF-κBp65and IL-6in OLP cell model.200nmol/L15-epi-LXA4can significantly reduce the expression ofthe NF-κBp65and IL-6(P<0.05).Conclusions(1)ALX-R protein was strongly expressed in NOM, but weakly in OLP.Meanwhile, ALX-R was negatively correlated with NF-κBp65, which indicate ALX-Rdefection may paly a certain role in OLP onset.(2) ALX-R expression in erosive type was not significantly different fromreticulate type, whereas the expression of NF-κBp65is significantly higher in erosivetype than reticulate type, which can be explained by the reason that NF-κBp65controls many inflammatory factors. Also, this result is consistent with erosive type oforal lichen planus is more severe in clinic.(3) When LPS-induced OLP inflammation HacaTs model was intervened by LXA4analogs, NF-κBp65signaling pathway was inhibited and the expression ofinflammatory mediators IL-6was decreased in dose-dependent manner, which givesus new ideas for the treatment of oral lichen planus, however, more researches need tobe done.