n-caproylsphingosine and Inflammation

Inflammation plays a critical role during benign prostatic hyperplasia (BPH) development. Danzhi qing'e (DZQE) decoction is a traditional Chinese medicine that has been widely used for estrogen and androgen-related diseases. However, its effect on inflammation-related BPH remains unclear.. To investigate the effect of DZQE on inhibition of inflammation-related BPH, and further identify the possible mechanism involved.. Experimental autoimmune prostatitis (EAP)-induced BPH was established and then 2.7 g/kg of DZQE was administrated orally for 4 weeks. The prostate sizes, weights and prostate index (PI) values were recorded. Hematoxylin and eosin (H&E) was performed for pathological analyses. Macrophage infiltrate was evaluated by Immunohistochemical (IHC). The inflammatory cytokine levels were measured by Rt-PCR and ELISA methods. The phosphorylation of ERK1/2 was examined by Western blot. The expression differences of mRNA expressions between EAP-induced and oestrogen/testosterone (E2/T)-induced BPH was investigated by RNA sequencing analyses. In vitro, human prostatic epithelial BPH-1 cells were stimulated with the conditioned medium from monocyte THP-1-derived M2 macrophages (M2CM), followed by treatment of Tanshinone IIA (Tan IIA), Bakuchiol (Ba), ERK1/2 antagonist PD98059 or ERK1/2 agonist C6-Ceramide. The ERK1/2 phosphorylation and cell proliferation were then detected by Western blotting and CCK8 assay.. DZQE suppressed inflammation-associated BPH via regulation of ERK1/2 signal by Tan IIA and Ba.

Topics: Animals; Cytokines; Estrogens; Humans; Inflammation; Male; MAP Kinase Signaling System; Medicine, Chinese Traditional; Prostatic Hyperplasia; Rats; Signal Transduction

Lung epithelium plays a significant role in modulating the inflammatory response to lung injury. Airway epithelial cells are targeted by hydrogen peroxide (H(2)O(2)) and oxygen radicals, which are agents commonly produced during inflammatory processes. The mechanisms and molecular sites affected by H(2)O(2) are largely unknown but may involve the induction of sphingomyelin (SM) hydrolysis to generate ceramide, which serves as a second messenger in initiating an apoptotic response. Here we show that exposure of human airway epithelial (HAE) cells to 50 to 100 microM H(2)O(2) induces within 5 to 10 min a greater than 2-fold activation of neutral sphingomyelinase activity with concomitant SM hydrolysis, ceramide generation, and apoptosis. On the other hand, activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate inhibits both H(2)O(2)-induced ceramide production and apoptosis. The apoptotic response could be restored by the addition of 25 microM cell-permeant C6-ceramide. These findings indicate that ceramide, the product of SM hydrolysis, plays an important role in H(2)O(2)-induced apoptosis in HAE cells, and that PKC counteracts ceramide-mediated apoptosis in these cells. We suggest that the mediation of epithelial cell apoptosis by ceramide and its inhibition by PKC constitute a central mechanism by which inflammatory processes are modulated in the epithelium of the lung.

Topics: Apoptosis; Ceramides; Diglycerides; DNA Fragmentation; Enzyme Activation; Epithelial Cells; Humans; Hydrogen Peroxide; Hydrolysis; Inflammation; Lung; Membrane Lipids; Oxidative Stress; Protein Kinase C; Second Messenger Systems; Sphingomyelin Phosphodiesterase; Sphingomyelins; Sphingosine; Tetradecanoylphorbol Acetate