The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion.

Lung fibroblast proliferation and differentiation into myofibroblasts are pathological key events during development of lung fibrosis. Cyclic nucleotide signaling is described as a negative modulator of these cellular processes, and cyclic nucleotide degrading type 4 phosphodiesterases (PDE4) are important regulators of these pathways. In this study, we elucidated expression and the role of individual subtypes of PDE4 in primary normal human lung fibroblast (NHLF) in controlling cytokines-induced proliferation and conversion to myofibroblasts by short-interfering RNAs (siRNAs) induced knockdown.

Cytokine-dependent balance of mitogenic effects in primary human lung fibroblasts related to cyclic AMP signaling and phosphodiesterase 4 inhibition.

Interleukin-1beta (IL-1beta) and basic fibroblast growth factor (bFGF) are important regulators of proliferation, and their expression is increased in lungs of patients with asthma, idiopathic pulmonary fibrosis (IPF), or chronic obstructive pulmonary disease (COPD). We investigated the effect of IL-1beta and bFGF on proliferation of human lung fibroblasts and the role of COX-2, PGE(2), and cAMP in this process. Furthermore, the effect of phosphodiesterase (PDE) 3 and 4 inhibition was analyzed.

Systematic expression profiling of the gastric H+/K+ ATPase in human tissue.

Objective: The potassium-competitive acid blockers (P-CABs), comprise a new, innovative group of competitive and reversible inhibitors of the gastric H+/K+ ATPase. Our aim was to identify sites of expression of the H+/K+ ATPase that are potential targets of these compounds by examining the expression profile of the gastric H+/K+ ATPase in the human body from a broad range of tissues.

Material And Methods: Expression profiling was done by quantitative mRNA analysis (TaqMan PCR).