TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation.
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been reported to induce keratinocyte apoptosis in vitro by engaging its sole receptor of fibroblast growth factor-inducible 14 (Fn14). In this study, we explored the role of TWEAK/Fn14 pathway in the growth of psoriatic keratinocytes that is, however, characterized by suppressed apoptotic cell death. Skin tissues from the patients with psoriasis or healthy donors were determined for TWEAK and Fn14 expression, and primary keratinocytes were evaluated under the stimulation of psoriatic proinflammatory cytokines or plus TWEAK. The results showed that both TWEAK and Fn14 were highly expressed in psoriatic skins. Moreover, the stimulation of psoriatic cytokines enhanced Fn14 expression by keratinocytes in vitro, which expressed TNF receptor 2 predominantly and proliferated increasingly with the addition of TWEAK. Furthermore, TWEAK stimulation enhanced the synthesis of survivin, inhibitor of apoptosis protein 2 and cellular FLICE-inhibitory protein in lesional keratinocytes. Therefore, TWEAK/Fn14 interaction prefers to enhance proliferation but not apoptosis of keratinocytes under psoriatic inflammation. The activation of nuclear factor-κB signalling-dependent anti-apoptotic proteins and biased expression of TNF receptors may be responsible for such a novel principle in keratinocytes under psoriatic inflammation.
Department of Medicine, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.|Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Hong
H
Cheng
Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Meifeng
M
Xu
Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Xiaoming
X
Liu
Department of Dermatology, Hubei Maternity and Child Health Hospital, Wuhan, China.
Xiaoyan
X
Zou
Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China.
Na
N
Zhan
Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Yumin
Y
Xia
D017209:Apoptosis; D049109:Cell Proliferation; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D000077022:Survivin; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000378:metabolism*
C107489:BIRC5 protein, human; D000074049:Cytokine TWEAK; D016207:Cytokines; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D000077022:Survivin; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors
TWEAK/Fn14 pathway; inflammation; keratinocyte; proliferation; psoriasis