Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association between tissue damage, chronic inflammation and cancer is well known. However, the underlying mechanisms are unclear. Here we characterize a mouse model in which constitutive epidermal extracellular-signal-regulated kinase-MAP-kinase signalling results in epidermal inflammation, and skin wounding induces tumours. We show that tumour incidence correlates with wound size and inflammatory infiltrate. Ablation of tumour necrosis factor receptor (TNFR)-1/-2, Myeloid Differentiation primary response gene 88 or Toll-like receptor (TLR)-5, the bacterial flagellin receptor, but not other innate immune sensors, in radiosensitive leukocytes protects against tumour formation. Antibiotic treatment inhibits, whereas injection of flagellin induces, tumours in a TLR-5-dependent manner. TLR-5 is also involved in chemical-induced skin carcinogenesis in wild-type mice. Leukocytic TLR-5 signalling mediates upregulation of the alarmin HMGB1 (High Mobility Group Box 1) in wound-induced papillomas. HMGB1 is elevated in tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease characterized by chronic skin damage. We conclude that in our experimental model the combination of bacteria, chronic inflammation and wounding cooperate to trigger skin cancer.
...
PMID:Innate sensing of microbial products promotes wound-induced skin cancer. 2557 23

In our previous study, we have found increased serum levels of HMGB1 in patients with Henoch- Schonlein purpura (HSP), allergic vasculitis (AV), and urticarial vasculitis (UV) and altered HMGB1 distribution in lesional skin in patients with HSP. HMGB1 plays a pro-inflammatory role in the pathogenesis of HSP. To further investigate the role of HMGB1 in the pathogenic mechanism of vasculitis, we investigated the anti-inflammatory effects of HMGB1 blockades (including anti-HMGB1 mAb and glycyrrhizin) in a mouse model of a cutaneous reverse passive Arthus (RPA) reaction. A total of 36 balb/c mice were randomly divided into four groups: the control group, IC model group, HMGB1 monoclonal antibody (anti-HMGB1-mAb) group and the glycyrrhizin group, with nine mice in each group. A cutaneous RPA reaction mouse model was established by injections of the OVA antibody and the OVA antigen. Mice of the anti-HMGB1-mAb group and glycyrrhizin group were pre-treated with anti-HMGB1 mAb or glycyrrhizin, respectively, before the RPA reaction. Our results indicated that HMGB1 blockades (anti-HMGB1 mAb and glycyrrhizin) obviously extenuated the severity of vasculitis skin damage and improved the histological evolvement of inflammatory cells infiltration, vascular fibroid necrosis, and vasodilation in a cutaneous RPA reaction mouse model. In addition, HMGB1 blockades reduced the infiltration of neutrophils, DCs, and T cells and decreased the mRNA expression of IL-6 and CCL5 in skin lesions in the cutaneous RPA reaction mouse model. We suggest that HMGB1 blockades may represent a new direction for the treatment of cutaneous vasculitis.
 ...
PMID:The Anti-inflammatory Effects of HMGB1 Blockades in a Mouse Model of Cutaneous Vasculitis. 3313 61