h 上游充通大学 Biology of glucocorticoids Shanghai Jiao Tong University Stress Hypothalamus CRH① Adrenal glands Inflammatory Anterior genes pituitary Prolactin p Translation D POMCH Chronic ACTH① Kidneys inflammation Transcription 4人①？ Adrenal cortex Adrenal Gland H&E capsule Infection/insult Glucocorticoids D Thymocyte and Induction of gluconeogenic T cell apoptosis enzymes(TAT↑，PEPCK↑) (de novo gene synthesis) Proliferation of erythroblasts Eosinophil/monocyte ⊙？ apoptosis Lung Bone metabolism T cell,eosinophil and development (osteocalcin↓) smooth muscle proliferation Collagenase-3(MMP-13) (cyclin D:3↓) Gelatinase B(MMP9)↓ Newton,Thorax 2000:55:603-613
Shanghai Jiao Tong University Newton, Thorax 2000; 55:603-613 Biology of glucocorticoids
上游充通大睾 Mechanisms of Glucocorticoid Action Shanghai Jiao Tong University Cytokine Glucocorticoid pm hsp hsp 1. Inhibit the production of 90 90 proinflammatory GR cytokines 2. Promote the production GR hsp hsp Inflammatory 90 90 protein of inflammatory Anti- cytokines inflammatory protein () () 3. Induce apoptosis in inflammatory cells K3 /VV几AAAAAA AAAAAA 4. Interfere with cytokine signals nm GR GR Anti-inflammatory protein gene TF TF TF binding site Inflammatory protein gene Newton,Thorax 2000;55:603-613
Shanghai Jiao Tong University Newton, Thorax 2000;55:603-613 Mechanisms of Glucocorticoid Action 1. Inhibit the production of proinflammatory cytokines 2. Promote the production of inflammatory cytokines 3. Induce apoptosis in inflammatory cells 4. Interfere with cytokine signals
Glucocorticoid-sensitive sites of 上泽充通大睾 后 Shanghai Jiao Tong University the immune response proliferation differentiatio MHC Class I/peptides- CD8 T-cell ◆ CD8 cytolytic T-cels APCs GC IL-2 GC MHCCaspid头 proliferation CD4 T-cell APCs CD4 immune celX L-1 (helper T-cells) (delayed hypersensitivity L-1,4,5,-6 Protein antigen- B-cell Plasma cell proliferation ↓ differentiation antibody production
Shanghai Jiao Tong University Glucocorticoid-sensitive sites of the immune response MHC Class I/peptides APCs MHC Class II/peptides APCs Protein antigen CD8 T-cell CD4 T-cell (helper T-cells) B-cell Plasma cell CD8 cytolytic T-cells CD4 immune cell (delayed hypersensitivity antibody production proliferation & differentiation proliferation proliferation & differentiation GC X X GC X X