title: LL-37 suppresses sodium nitroprusside-induced apoptosis of systemic sclerosis dermal fibroblasts.
abstract: 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 E(2) (PGE(2)). 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.
authors: Hee Jung
authors: HJ
authors: Kim
authors: Dae Ho
authors: DH
authors: Cho
authors: Kyung Jin
authors: KJ
authors: Lee
authors: Chul Soo
authors: CS
authors: Cho
authors: Sa Ik
authors: SI
authors: Bang
authors: Baik Kee
authors: BK
authors: Cho
authors: Hyun Jeong
authors: HJ
authors: Park
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D012595:Scleroderma, Systemic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D009599:Nitroprusside; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D054804:Cathelicidins