During angiogenesis, new vessels emerge from existing endothelial lined vessels to promote the degradation of the vascular basement membrane and remodel the extracellular matrix (ECM), followed by endothelial cell migration, and proliferation and the new generation of matrix components. Matrix metalloproteinases (MMPs) participate in the disruption, tumor neovascularization, and subsequent metastasis while tissue inhibitors of metalloproteinases (TIMPs) downregulate the activity of these MMPs. Then, the angiogenic response can be directly or indirectly mediated by MMPs through the modulation of the balance between pro-and anti-angiogenic factors. This review analyzes recent knowledge on MMPs and their participation in angiogenesis.

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Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72. The aim of this study was to explore the pathways of phosphorylation and overexpression of the SRP72 polypeptide, using an in vitro model of Jurkat cells stimulated by recombinant human (rh)IL-1β in the presence of MAPK inhibitors. We used Jurkat cells as a substrate stimulated with rhIL-1β in the presence of MAPK inhibitors at different concentrations in a time course in vitro experiment by immunoprecipitation, immunoprecipitation-Western blotting, and real time PCR. Our results showed that rhIL-1β causes up-regulation of protein expression and phosphorylation of SRP72 in Jurkat cells. Inhibitors of the MAPK pathway ERK1/2 or p38α/β down-regulate the expression of SRP72 autoantigen in Jurkat cells stimulated by rhIL-1β. Our results highlight the importance of studying the pathways of activation and overexpression of autoantigens. It will be necessary to perform careful research on various kinases pathways, including MAPK in dermatomyositis and other rheumatic diseases, to help to explain the routes of activation and inhibition of autoantigens. The understanding of this process may help to develop new therapies to prevent and control the loss of tolerance toward own normal proteins.

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The present study aimed to examine the immunomodulatory properties of the methanolic (MeOH) extract from Pouteria. campechiana leaves in peritoneal macrophages of Balb/c mice. Peritoneal macrophages isolated from mice and Vero cells were treated with the MeOH extract from leaves. Cell viability of the macrophages and Vero cells were evaluated by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The phagocytic activity, as nitric oxide (NO), hydrogen peroxide (H 2 O 2 ), interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α) production were evaluated on peritoneal macrophages. Results showed that the MeOH extract from leaves was able to stimulate the phagocytic activity and increase NO, H 2 O 2 and cytokines production. The viability assays do not show cytotoxic effect on cell viability and cause a significative proliferative effect in the macrophages of a concentration-dependent manner. These results conclude that the MeOH extract from P. campechiana leaves possessed a stronger immunostimulatory effect in a concentration-dependent manner without affect the cell viability.

The aim of this work was to evaluate the potential anti-inflammatory effect of protein hydrolysate and peptide fractions from Salvia hispanica L. seeds. Protein isolate was obtained using defatted flour of mucilage-free seeds. Hydrolysis process was conducted by enzymatic digestion. The hydrolysate was fractionated using ultrafiltration membranes to obtain the peptide fractions (<1, 1-3, 3-5, 5-10, and >10 kDa). Protein derivatives were evaluated by in vitro activation of murine peritoneal macrophages. The antiinflammatory activity was determined as NO production, H 2 O 2 release and pro-and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) production. All the peptides exerted an antiinflammatory activity, but peptide fraction between 1-3 kDa showed the highest anti-inflammatory effect. This fraction was evaluated on in vivo murine models of TPA-induced ear edema and DNFB-induced delayed-type hypersensitivity, exhibiting inhibitory effects. Hence, the results demonstrated that protein derivatives from S. hispanica L. seeds have in vitro and in vivo antiinflammatory effects.

Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti-inflammatory effects of TFD (0.1-200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The in vivo anti-inflammatory activity of TFD was assessed using the carrageenan-induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced-writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF-α (IC = 5.66 µM) and IL-6 (IC = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti-inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED = 48.2 mg/kg) and the phase 2 (ED = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED = 32.3 mg/kg) with similar potency compared to naproxen (ED = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co-administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti-inflammatory activity and in vivo antinociceptive effects.