PMID- 28620393 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - TWEAK/Fn14 Activation Participates in Ro52-Mediated Photosensitization in Cutaneous Lupus Erythematosus. PG - 651 LID - 10.3389/fimmu.2017.00651 [doi] LID - 651 AB - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines. The chemotaxis of J774.2 macrophages was evaluated on TWEAK stimulation of cocultured keratinocytes. We found that TWEAK, Fn14, and downstream cytokines were highly expressed in CLE lesions that overexpressed Ro52. Moreover, TWEAK enhanced the UVB-induced Ro52 upregulation in murine keratinocytes. Meanwhile, TWEAK stimulation of keratinocytes favored the migration of macrophages through promoting the production of chemokine C-C motif ligands 17 and 22. Furthermore, Fn14 siRNA transfection or nuclear factor-kappa B (NF-kappaB) inhibitor abrogated the TWEAK enhancement of Ro52 expression in keratinocytes. Similarly, TNF receptor associated factor 2 (TRAF2) siRNA reduced the protein level of Ro52 in these cells upon TWEAK stimulation. Interestingly, UVB irradiation increased the expression of TNF receptor type 1 (TNFR1) but not affecting TNFR2 expression in keratinocytes. In conclusion, the TWEAK/Fn14 signaling participates in Ro52-mediated photosensitization and involves the activation of NF-kappaB pathway as well as the function of the TRAF2/TNFR partners. FAU - Liu, Yale AU - Liu Y AD - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Xu, Meifeng AU - Xu M AD - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Min, Xiaoyun AU - Min X AD - Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Wu, Kunyi AU - Wu K AD - Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Zhang, Ting AU - Zhang T AD - Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Li, Ke AU - Li K AD - Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Xiao, Shengxiang AU - Xiao S AD - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. FAU - Xia, Yumin AU - Xia Y AD - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. LA - eng PT - Journal Article DEP - 20170531 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC5449764 OTO - NOTNLM OT - Fn14 OT - Ro52 OT - TWEAK OT - cutaneous lupus erythematosus OT - keratinocyte OT - photosensitization OT - tumor necrosis factor receptor OT - ultraviolet B EDAT- 2017/06/18 06:00 MHDA- 2017/06/18 06:01 PMCR- 2017/01/01 CRDT- 2017/06/17 06:00 PHST- 2017/02/27 00:00 [received] PHST- 2017/05/17 00:00 [accepted] PHST- 2017/06/17 06:00 [entrez] PHST- 2017/06/18 06:00 [pubmed] PHST- 2017/06/18 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.00651 [doi] PST - epublish SO - Front Immunol. 2017 May 31;8:651. doi: 10.3389/fimmu.2017.00651. eCollection 2017.