title: Role of Toll-like receptor 4 signaling in cutaneous chronic graft-versus-host disease.
abstract: Cutaneous damage is one of the characterized manifestations in chronic graft-versus-host disease (cGVHD). When local effective immunity in the skin is altered to a dysimmune reaction, cutaneous injuries occur. Toll-like receptor 4 signaling is regarded as a central mediator of inflammation and organ injury. In this study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous cGVHD was markedly increased compared with that from non-GVHD patients and healthy controls. In addition, NF-κB expression, TLR4 downstream signaling, and TLR4-mediated cytokines, including IL-6 and ICAM-1, were upregulated. Moreover, ICAM-1 was widely distributed in skin biopsies from patients with cutaneous cGVHD. We also found that LPS induced TLR4-mediated NF-κB activation and IL-6 and ICAM-1 secretion in human fibroblasts in vitro. Thus, TLR4, NF-κB, IL-6, and ICAM-1 contribute to the inflammatory response that occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for cutaneous cGVHD therapy.
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Peilong
authors.initials: P
authors.lastname: Lai
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Chenwei
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Suijing
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ling
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Zesheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1
keywords: IL-6; Toll-like receptor 4; chronic graft-versus-host disease; cutaneous graft-versus-host disease; intercellular adhesion molecule-1