Synovial fibroblasts, established in culture from patients with RA, were treated with proinflammatory cytokines and prostaglandin E(2) (PGE(2)) for 24 h. These cells enhanced the production and the messenger RNA expression of PTH-related peptide (PTHrP) using proinflammatory cytokines, such as interleukin (IL)-1alpha, tumor necrosis factor-alpha without the coordination of other cytokines. In a...

Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each chemical mediator have been demonstrated with neutrophils in vitro, how such chemical mediators act cooperatively or counteractively in vivo remains largely unknown. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance ene...

Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC exp...

Hepatic stellate cells (HSCs) are critical mediators of immunosuppression and the pathogenesis of hepatocellular carcinoma (HCC). Our previous work indicates that HSCs promote HCC progression by enhancing immunosuppressive cell populations including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). MDSCs are induced by inflammatory cytokines (e.g., prostaglandins) and are...

Evidence is accumulating that group 2 innate lymphoid cells (ILC2) play an important role in allergic airway inflammation by producing a large amount of type 2 cytokines. But it remains poorly understood how its activities are properly controlled in vivo. Here, we demonstrated that prostaglandin E2 (PGE2) had a profound inhibitory effect on IL-33-induced ILC2 expansion and IL-5 and IL-13 produc...

PURPOSE We explored the anti-inflammatory effects of doxycycline in experimental uveitis and the underlying mechanisms. METHODS Rats with endotoxin-induced uveitis (EIU) received doxycycline (1.5 mg/kg) or the control vehicle via intraperitoneal injection. Clinical scores were graded under a slit lamp. Rat peritoneal macrophages were used in vitro to further explore the anti-inflammatory mech...

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometas...

Prostaglandin E2 (PGE2) is a lipid mediator that modulates the function of myeloid immune cells such as macrophages and dendritic (DCs) through activation G protein-coupled receptors EP2 EP4. While both EP4 signaling leads to an elevation intracellular cyclic adenosine monophosphate (cAMP) levels stimulating Gα s protein, also couples inhibitory i protein decrease production cAMP. The receptor-...

Prostaglandin E2 (PGE2) can increase endothelial vascular endogrowth factor A (VEGF-A) production but the mechanisms involved are unclear. Here we characterized the transcriptional mechanisms involved in human airway smooth muscle cells (HASMC). PGE2 increased VEGF-A mRNA and protein but not mRNA stability. PGE2 stimulated the activity of a transiently transfected 2068-bp (-2018 to +50) VEGF-A ...

After synthesis and release from cells, prostaglandin E2 (PGE2) undergoes reuptake by the prostaglandin transporter (PGT), followed by cytoplasmic oxidation. Although genetic inactivation of PGT in mice and humans results in distinctive phenotypes, and although experiments in localized environments show that manipulating PGT alters downstream cellular events, a direct mechanistic link between P...