The role of heat shock protein 70 in mouse contact hypersensitivity model
열충격 단백 70 (Heat shock protein 70) 이 마우스 모델 접촉성 과민반응증에 미치는 영향
Dept. of Medicine/박사
Allergic contact dermatitis (ACD) is one of the most common skin diseases through contact hypersensitivity (CHS). In CHS, multiple cells, inflammatory mediators, and cytokines are known to be involved to regulate the immune response. In previous study, I revealed the reactive oxygen species (ROS) generation by 2, 4, 6-trinitrobenzene sulfomic acid (TNBS) in mouse dendritic cells, XS-106 cells, followed by ATP synthase carbonylation. Also I identified the carbonylation of heat shock protein 70 (Hsp70) and exogenous antioxidant role of protein transduction domain fused Hsp70 (PTD-Hsp70) which lowered ROS and IL-12 generation in TNBS treated XS-106 cells. In this study, I investigated the role of Hsp70 in contact hypersensitivity (CHS) using PTD-Hsp70 in BALB/c mice. PTD-Hsp70 pretreatment: (i) suppressed ear swelling; (ii) down-regulated phosphorylated p38 but up-regulated phosphorylated extracellular signal regulated kinase; (iii) increased the populations of CD4+CD25+ T cells and CD4+CD25+Foxp3+ T cells; (iv) decreased the secretion of tumor necrosis factor-α (TNF-α), interlukin (IL)-12, interferon-γ and IL-2 but up-regulated IL-4, IL-17, IL-23 and transforming growth factor beta (TGF-β) at challenge phase in drainage lymph node (dLN); (v) down- regulated IL-6 and IL-12 but up-regulated IL-4, IL-23 and TGF-β at challenge phase in ear tissue. This experiment suggests that PTD-Hsp70 attenuates contact hypersensitivity. In summary, PTD-Hsp70 (i) regulates the mitogen activated protein kinase (MAPK) pathway which in turn prevents inflammation and apoptosis; (ii) down-regulates primary inflammatory cytokines and Th1 cell differentiation; (iii) regulates through Th2 mediated cytokines; (iv) increases TGF-β and regulatory T cells; and (v) may deprived pathognomic role of Th17 related to inflammation. In conclusion, topical application of PTD-Hsp70 attenuates CHS through MAPK pathway and regulating Th1 cytokines, Th2 cytokines, and regulatory T cells.