LL-37 suppresses sodium nitroprusside-induced apoptosis of systemic sclerosis dermal fibroblasts

: The human cathelicidin antimicrobial peptide LL‐37 regulates apoptosis of several cell types. Defective apoptosis of skin fibroblasts may contribute to systemic sclerosis (SSc). Here, we show that LL‐37 inhibited apoptosis of SSc fibroblasts and identified the signalling pathways by which LL‐37 mediates apoptosis. Immunohistochemistry showed that cathelicidin expression was enhanced in SSc patients compared with healthy controls. In addition, LL‐37 decreased sodium nitroprusside (SNP)‐induced apoptosis of SSc fibroblasts. LL‐37 significantly increased expression of Bcl‐2 and decreased levels of BAX protein. Pretreatment with LL‐37 decreased activation of caspase‐3 following SNP‐treatment. Moreover, exposure of SSc fibroblasts to LL‐37 resulted in increased expression of COX‐2 and stimulation of prostaglandin E2 (PGE2). Furthermore, LL‐37 induced phosphorylation of ERK and the ERK inhibitor PD98059 blocked the inhibitory effect of LL‐37 on apoptosis. Our data indicate that LL‐37 may be associated with skin sclerosis by inhibiting apoptosis of dermal fibroblasts.