u-62840 and Inflammation
u-62840 has been researched along with Inflammation* in 2 studies
Other Studies
2 other study(ies) available for u-62840 and Inflammation
Article | Year |
---|---|
Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers.
Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing.. We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization.. uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution.. This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans. Topics: Animals; Collagen; Disease Models, Animal; Epoprostenol; Humans; Inflammation; Iontophoresis; Mice; Scleroderma, Localized; Scleroderma, Systemic; Skin; Ulcer; Wound Healing | 2022 |
The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages.
Primary pulmonary hypertension (PPH) is characterized by increased pulmonary arterial pressure and vascular resistance. We and others have observed that inflammatory cytokines and infiltrates are present in the lung tissue, but the significance is uncertain. Treprostinil (TRE), a prostacyclin analogue with extended half-life and chemical stability, has shown promise in the treatment of PPH. We hypothesize that TRE might exert beneficial effects in PPH by antagonizing inflammatory cytokine production in the lung. Here we show that TRE dose-dependently inhibits inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and granulocyte macrophage colony-stimulating factor) secretion and gene expression by human alveolar macrophages. TRE blocks NFkappaB activation, but IkappaB-alpha phosphorylation and degradation are unaffected. Moreover, TRE does not affect the formation of the NFkappaB.DNA complex but blocks nuclear translocation of p65. These results are the first to illustrate the anti-cytokine actions of TRE in down-regulating NFkappaB, not through its inhibitory component or by direct binding but by blocking nuclear translocation. These data indicate that inflammatory mechanisms may be important in the pathogenesis of PPH and cytokine antagonism by blocking NFkappaB may contribute to the efficacy of TRE therapy in PPH. Topics: Active Transport, Cell Nucleus; Adolescent; Adult; Antihypertensive Agents; Cell Adhesion; Cell Nucleus; Cytokines; Dose-Response Relationship, Drug; Down-Regulation; Epoprostenol; Humans; Inflammation; Interleukin-6; Interleukins; Lung; Macrophages; Middle Aged; NF-kappa B; Protein Binding; Protein Transport; Time Factors; Transcription Factor RelA | 2002 |