BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are...

Dynorphins (dyn) are a major class of endogenous opioid peptides that modulate the functions of immune cells. However, the effects of dyn on the immune functions of glial cells in the central nervous system (CNS) have not been well characterized. Because nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) produced by glial cells are involved in various phy...

Tumor necrosis factor alpha (TNF-alpha) is important in resistance to various microorganisms and provides signals to the target cells through two different receptors, TNF-alpha receptor I (TNFRI) (p55 receptor) and TNFRII (p75 receptor). To delineate the significance of the two different signaling pathways in resisting infections with extracellular bacteria, we examined the resistance of mice t...

The lung collectin surfactant protein A (SP-A) has both anti-inflammatory and pro-phagocytic activities. We and others have previously shown that SP-A inhibits the macrophage production of TNF-α stimulated by the gram negative bacterial component lipopolysaccharide (LPS). We propose that SP-A decreases the production of proinflammatory cytokines by alveolar macrophages via a CD14 independent me...

We recently reported that mast cells stimulated via FcepsilonRI aggregation can enhance T cell activation by a TNF-dependent mechanism. However, the molecular mechanisms responsible for such IgE-, Ag- (Ag-), and mast cell-dependent enhancement of T cell activation remain unknown. In this study we showed that mouse bone marrow-derived cultured mast cells express various costimulatory molecules, ...

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in malignancy. However, the role and regulation of PTHrP in normal physiology is just beginning to be explored. PTHrP is found in the spleen and has several other features common to cytokines. Since endotoxin (LPS) causes many of its effects indirectly by inducing cytokines, studies were undertaken to determine whether LPS might a...

TNF-α is known to induce a strong up-regulation of Fas expression in mouse Sertoli cell cultures, leading to their apoptosis triggered by effector FasL-bearing cells. These data suggest that increased Fas expression on the cell surface might be a key event in the pathogenesis of autoimmune orchitis, by inducing a leakage of the blood-tubular barrier as a consequence of Sertoli cell apoptosis. I...

BACKGROUND Despite the significant health impact of olfactory loss in chronic rhinosinusitis (CRS), the underlying pathophysiology is incompletely understood. A transgenic mouse model of olfactory inflammation induced by tumor necrosis factor-alpha (TNF-α) has provided new insights into the cellular and molecular basis of inflammatory olfactory loss. Here, we utilize systemic corticosteroids to...