title: Increased expression of NLRP3 inflammasome components and interleukin-18 in patients with bullous pemphigoid.
abstract: BACKGROUND
  Bullous pemphigoid (BP) is the most common blistering autoimmune disease severely affecting older people. The complex interplay between innate and adaptive immunity is critical in the development of BP. Inflammasomes, which lead to cleavage-induced maturation of pro-inflammatory cytokines, have been shown to participate in a variety of autoimmune diseases. However, the role of inflammasomes in BP has not been delineated.
  
  
  OBJECTIVE
  The present work aimed to investigate whether inflammasomes are involved in the pathogenesis and progression of BP.
  
  
  METHODS
  Expressions of inflammasome components at the messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from patients with BP and from healthy controls were investigated by quantitative real-time PCR (qRT-PCR) and western blot, respectively. ELISA was employed to evaluate interleukin (IL)-1β, IL-18, lactate dehydrogenase (LDH), and high-mobility group-1 (HMGB1) levels in the serum and blister fluid of patients with BP. Immunohistochemical staining was used to detect IL-18 expression in the skin lesion of patients with BP.
  
  
  RESULTS
  The mRNA levels of NLRP3 inflammasome components (NLRP3, pro-caspase-1, and pro-IL-18) in PBMCs were significantly up-regulated in BP patients compared with those in healthy controls, and were positively correlated with the autoantibody titers for BP180-NC16A. Western Blot analysis showed that the baseline expressions of NLRP3 inflammasome components were increased in PBMCs of BP patients compared with healthy controls, and we failed to observe the mature IL-1β and IL-18. Further analysis showed that IL-18 was elevated in serum, blister fluid and lesional skin from patients with BP, and the serum IL-18 level was positively correlated with the titers of anti-BP180-NC16A autoantibody in BP patient. Most importantly, we found that mRNA expressions of the NLRP3-caspase-1-IL-18 axis components and the serum IL-18 level in BP patients decreased dramatically after effective treatment, which indicated that the up-regulation of NLRP3 inflammasome was responsible, at least to a great degree, for the enhanced IL-18 level in BP patients.
  
  
  CONCLUSIONS
  This study demonstrates that the expression of the NLRP3-caspase-1-IL-18 axis is highly expressed in the PBMCs of patients with BP, and correlated with disease activity, suggesting its involvement in the pathogenesis and progression of BP.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi'an 710032, China. Electronic address: xjwgang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000097:blood / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood; D045022:Lactate Dehydrogenases / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D020170:Caspase 1; D024243:HMGB1 Protein; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D045022:Lactate Dehydrogenases; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C585491:HMGB1 protein, human; C000589760:IL18 protein, human; C508585:IL1B protein, human; C453881:NLRP3 protein, human
keywords: Autoimmune disease; Bullous pemphigoid; Interleukin-18; NLRP3 inflammasome