Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in photorejuvenation and inflammatory acne vulgaris.

Background: Nonablative lasers are widely used for treatment of wrinkles, atrophic scars and acne. These lasers stimulate dermal remodelling and collagen production, but the early molecular stimulus for this is unknown. The mechanism of nonablative lasers in inflammatory acne is variously suggested to be damage either to sebaceous glands or to Propionibacterium acnes.

Rolipram, salbutamol and prostaglandin E2 suppress TNFalpha release from human monocytes by activating Type II cAMP-dependent protein kinase.

The extent to which cAMP-dependent protein kinase (PKA) mediates the inhibitory effects of cAMP-elevating drugs on tumour necrosis factor (TNF) alpha release from lipopolysaccharide (LPS)-stimulated human monocytes is equivocal. Here, we have investigated the role of this kinase by exploiting the ability of certain novel cAMP analogues to inhibit or activate PKA and the recently described cAMP-guanine nucleotide-exchange factors (GEFs). Pre-treatment of monocytes with Rp-8-Br-cAMPS, a selective inhibitor of Type I PKA that has no effect on basal or stimulated Rap1 (a downstream effector of cAMP-GEFs) activity, potentiated LPS-induced TNFalpha output but had little or no effect on the suppression of this cytokine effected by rolipram (a PDE4 inhibitor), prostaglandin (PG) E2 and salbutamol (a beta2-adrenoceptor agonist).

Suppression of granulocyte/macrophage colony-stimulating factor release from human monocytes by cyclic AMP-elevating drugs: role of interleukin-10.

1. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by cells of the monocyte/macrophage lineage and has been implicated in the pathogenesis of bronchitis and asthma. 2.

p38 MAP kinase and MKK-1 co-operate in the generation of GM-CSF from LPS-stimulated human monocytes by an NF-kappa B-independent mechanism.

1. The extent to which the p38 mitogen-activated protein (MAP) kinase and MAP kinase kinase (MKK)-1-signalling pathways regulate the expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) from LPS-stimulated human monocytes has been investigated and compared to the well studied cytokine tumour necrosis factor-alpha (TNF alpha). 2.

Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.

Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10).

Albuterol does not antagonize the inhibitory effect of dexamethasone on monocyte cytokine release.

Beta2-adrenoceptor agonists given by the inhaled route are the most effective bronchodilators known, yet high doses of these drugs may be associated with an increase in asthma mortality and morbidity. One theory for this paradox is that chronic use of beta2-adrenoceptor agonists compromises the anti-inflammatory action of glucocorticosteroids. This hypothesis derives from the ability of albuterol and fenoterol to inhibit the interaction of the glucocorticosteroid receptor (GR) with proinflammatory transcriptional activators acting on the promoter region of certain target genes that encode cytokines such as tumor necrosis factor-alpha (TNF alpha) and granulocyte/macrophage colony-stimulating factor (GM-CSF).

Release of granulocyte-macrophage colony stimulating factor by human cultured airway smooth muscle cells: suppression by dexamethasone.

Smooth muscle cells represent a significant percentage of the total cells in the airway but their contribution to the inflammatory response seen in airway disease has not been studied. Hence, we have looked at the release of the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in response to bacterial lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). Human airway smooth muscle (HASM) cells released GM-CSF under basal conditions (45.

Suppression of lipopolysaccharide-induced tumor necrosis factor-alpha generation from human peripheral blood monocytes by inhibitors of phosphodiesterase 4: interaction with stimulants of adenylyl cyclase.

We assessed the role of cyclic nucleotides in modulating lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) generation in human peripheral blood monocytes. Exposure of monocytes to LPS (3 ng/ml) evoked a delayed, time-dependent generation of TNF-alpha that reached a maximum level 5-6 hr after LPS challenge and remained constant for up to 24 hr. This effect was concentration dependent and resulted in a 20-40-fold increase in the release of TNF-alpha that was sensitive to actinomycin D and cycloheximide.

Pharmacological characterization of a receptor for platelet-activating factor on guinea pig peritoneal macrophages using [3H]apafant, a selective and competitive platelet-activating factor antagonist: evidence that the noncompetitive behavior of apafant in functional studies relates to slow kinetics of dissociation.

In this paper we report the characterization of a receptor for platelet-activating factor (PAF) on guinea pig peritoneal macrophages, using a radiolabeled hydrophilic PAF antagonist, [3H] apafant. [3H]Apafant bound to intact macrophages in a concentration-dependent manner that was specific, saturable, reversible, and inhibited competitively by C18-PAF (1-O-octadecyl-2-O-acetyl-sn-glyceryl- 3-phosphocholine). Scatchard transformation and Hill analysis of these data revealed that [3H]apafant identified a homogeneous population of noninteracting sites with a pKd of 8.