The Molecular Mechanism By Which Lipoteichoic Acid Modulates Propionibacterium Acnes-induced Inflammation

Acnes almost become epidemic among young people.Patients who suffer from recurrent bouts of acnes are in great pain.Therefore,it is urgent to find effective drugs to treat acnes.Previously,we found that lipoteichoic acid(LTA),a component of cell wall of gram-positive bacteria,inhibited inflammation induced by P.acnes.However,the underlying mechanism by which LTA modulates P.acnes-induced inflammation remains unknown.Here I first explored the mechanism by which P.acnes induced the expression of inflammatory cytokines in keratinocytes.P.acnes induced pro-inflammatory cytokines via the activation of TLR2,and silencing miR155 and IL-29 decreased the expression of pro-inflammatory cytokines such as TNF-? and IL-6.Moreover,TLR2 deficiency decreased miR155 and IL-29 expression induced by P.acnes,and IL-29 expression was down-regulated after miR155 silencing.These results suggest that P.acnes induces inflammatory responses by the activation of TLR2-miRl 55-IL-29 signaling pathway in keratinocytes.Secondly,I confirmed that LTA inhibited P.acnes-induced inflammation.The inhibitory effect of LTA on P.acnes-induced inflammation was dependent on miR143,as the inhibition of miR143 increased P.acnes-induced inflammatory cytokines expression while the overexpression of miR143 abrogated the inhibitory effect of LTA on P.acnes-induced inflammation.In addition,miR143 inhibitor restored the expression of P.acnes-induced inflammatory cytokines inhibited by LTA.Furthermore,miR143 did not inhibit TLR2 expression after miR1 43 binding sites in TLR2 3'UTR was mutated,suggesting that LTA induces miR143 expression,and then miR1 43 binds to TLR2 3'UTR to inhibit TLR2 expressionAt the end,I found that LTA induced TLR2 expression at early stage but inhibited TLR2 expression after 3 hours treatment.As a TLR2 ligand,LTA induced TLR2 expression before 3 hours and then upregulated miR143 expression.However,miR143 in turn bound to TLR2 3'UTR to silence TLR2 expression.Thereby the decrease of miR143 expression is in line with the reduction of TLR2 expression at the later stage.Altogether,these data demonstrate that P.acnes induces inflammation through the activation of TLR2-miR155-IL-29 signaling pathway.LTA induces miR143 expression by activation of TLR2 at early stage,and then miR143 inhibits TLR2 expression by targeting to TLR2 3'UTR at later stage.To our knowledge,our findings show for the first time that LTA modulates P.acnes-induced inflammation by targeting to its receptor TLR2 via the induction of miR143.This discovery will provide new insights into the treatment of acnes in the future.