Mometasone interacts with intravarycular receptors of glucocorticoids, facilitating the release of the receptor from binding to immunophilin and heat shock proteins 70 and 90. Penetration of the activated receptor into the nucleus, binding to glucocorticoid-sensitive regulatory elements of DNA - a specific effect on gene expression (activation and suppression). Interaction with other protein transcription factors, including NFκB and AP-1, regulating the expression of many proteins of the immune system, which leads to suppression of the expression of genes encoding some cytokines, collagenase and stromelysins.
The anti-inflammatory effect of mometasone is due to several factors.
1. The drug induces the synthesis of lipocortin, which inhibits the activity of phospholipase A2. Inhibition of phospholipase-mediated A2 hydrolysis of membrane phospholipids of damaged tissues prevents the formation of arachidonic acid. The disruption of the formation of arachidonic acid actually means inhibition of the synthesis of prostaglandins,since arachidonic acid is a substrate for further metabolism along the cyclooxygenase pathway, and also along the lipoxygenase pathway, with appropriate inhibition of leukotriene synthesis.
2. The anti-inflammatory effect of glucocorticoids is potentiated by their ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins in the inflammatory focus, including pro-inflammatory prostaglandins E2 and I2.
3. Mometasone inhibits the expression of molecules of intercellular adhesion in the endothelium of blood vessels, violating the penetration of neutrophils and monocytes into the focus of inflammation. After the introduction of glucocorticoids, an increase in the concentration of neutrophils in the blood (due to their entry from the bone marrow and the restriction of migration from the blood vessels) is noted. This causes a decrease in the number of neutrophils in the site of inflammation.
Mometasone inhibits the transcription of cytokine genes that stimulate the inflammatory and immune response (IL-1, IL-2, IL-6, IL-8), as well as tumor necrosis factor (and some others). Also, a decrease in the transcription rate and an increase in the degradation of the receptor genes for IL-1 and IL-2, inhibition of the transcription of the metalloproteinase (collagenase, elastase, etc.) genes involved in the increase permeability of the vascular wall, in the processes of scarring and destruction of cartilaginous tissue in diseases of the joints.
Immunosuppressive action is due to inhibition of transcription of DNA encoding the main histocompatibility complex, pro-inflammatory cytokines and inhibition of proliferation of T lymphocytes. It leads to a decrease in the number of T-lymphocytes and their influence on B-lymphocytes, inhibits the production of immunoglobulins. Reduces the formation and increases the decomposition of components of the complement system.
The antiallergic effect is associated with the inhibition of the synthesis of mediators of allergy, degranulation of mast cells and release of mediators of allergy, and therefore it is effective for allergic reactions of immediate type.
Salicylic acid causes exfoliation of the stratum corneum and, at the same time, does not lead to qualitative or quantitative changes in the structure of the viable epidermis. This mechanism of action is explained by dissolving the intercellular binder. Salicylic acid reduces the secretion of sebaceous and sweat glands. It also exhibits weak antimicrobial activity, keratoplastic action in low and keratolytic action in high concentrations.