Pneumonia is a leading cause of morbidity and mortality. While inflammation is a host protective response that ensures bacterial clearance, a finely regulated response is necessary to prevent bystander tissue damage. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a GC-induced protein with anti-inflammatory and proresolving bioactions, yet the therapeutical role of GILZ in infectious diseases remains unexplored. Herein, we investigate the role and effects of GILZ during acute lung injury (ALI) induced by LPS and Streptococcus pneumoniae infection. GILZ deficient mice (GILZ−/−) presented more severe ALI, characterized by increased inflammation, decreased macrophage efferocytosis and pronounced lung damage. In contrast, pulmonary inflammation, and damage were attenuated in WT mice treated with TAT-GILZ fusion protein. During pneumococcal pneumonia, TAT-GILZ reduced neutrophilic inflammation and prevented the associated lung damage. There was also enhanced macrophage efferocytosis and bacterial clearance in TAT-GILZ-treated mice. Mechanistically, TAT-GILZ enhanced macrophage phagocytosis of pneumococcus, which was lower in GILZ−/− macrophages. Noteworthy, early treatment with TAT-GILZ rescued 30% of S. pneumoniae-infected mice from lethal pneumonia. Altogether, we present evidence that TAT-GILZ enhances host resilience and resistance to pneumococcal pneumonia by controlling pulmonary inflammation and bacterial loads leading to decreased lethality. Exploiting GILZ pathways holds promise for the treatment of severe respiratory infections.

Aims: Perform the phytochemical analysis and investigate the spasmolytic activity of the hydroalcoholic extract obtained from S. cumini seeds (EHS-SC). Study Design: Qualitative phytochemical analysis and test of the EHS-SC on isolated smooth muscles (aorta, trachea, jejunum and uterus) of rat, to value effect relaxant and/or inhibitor. Place and Duration Methodology: EHS-SC was submitted to phytochemical analysis and changes in color, fluorescence and absence or presence of precipitate were observed. The smooth muscle segments were suspended (tension of 1 g) in glass vats containing specific saline solution, at an appropriate temperature and after stabilization period, was stimulated by a suitable contractile agent to observe the effect of EHS-SC in the phasic and/or tonic component. Original ResearchArticle the CCh to 82.9 ± 10.5; 67.6 ± 6.0 and 10.1 ± 8.3%. Conclusion: Spasmolytic activity may be combined with antimicrobial and antidiarrheal activity according to literature data, where they show that the seeds have the same secondary metabolites, signaling the therapeutic potential for the treatment of colic and/or diarrhea. The upward arrow represents the addition of CCh (carbachol). The down arrows represent the concentrations of nsion); min (minutes); W = washPeer-review history: The peer review history for this paper can be accessed here:

Syzygium cumini L. Skeels (Myrtaceae) commonly known as jambolan is used as traditional medicine to treat gastrointestinal disorders in children in Brazil. This work is one of the first to evaluate the antidiarrhoeal and antispasmodic activity of the standardized extract of S. cumini leaves (HESc) in experimental models in vitro and in vivo rodents. Mice pre-treated with HESc (100, 250 and 1000 mg/kg) and atropine (1.0 mg/kg) had reduced intestinal transit velocity of 11.0; 23.2 and19.1%, respectively compared to saline control (46.6±0.9). In isolated rats jejunum, HESc (50, 150 and 300 µg/mL) shifted to the right cumulative concentration-response curves to ACh with changing maximum effect (E max ), which is characteristic of non-competitive antagonism to ACh. HESc also promoted relaxation (E max 90.2±5.8%) in preparations pre-contacted with KCl (75 mM). Additionally, it reduced the maximal CaCl 2 -induced response in 15.4; 56.3 and 92.1% in a concentration-dependent manner. The study results show that HESc has an antidiarrhoeal and spasmolytic potential that can be partly explained by the reduction of intestinal transit velocity and blockage of the voltage-dependent calcium channels in the smooth intestinal muscle.

Macrophages are important effectors of inflammation resolution that contribute to the elimination of pathogens and apoptotic cells and restoration of homeostasis. Pre-clinical studies have evidenced the anti-inflammatory and pro-resolving actions of GILZ (glucocorticoid-induced leucine zipper). Here, we evaluated the role of GILZ on the migration of mononuclear cells under nonphlogistic conditions and Escherichia coli-evoked peritonitis. TAT-GILZ (a cell-permeable GILZ-fusion protein) injection into the pleural cavity of mice induced monocyte/macrophage influx alongside increased CCL2, IL-10 and TGF-β levels. TAT-GILZ-recruited macrophages showed a regulatory phenotype, exhibiting increased expression of CD206 and YM1. During the resolving phase of E. coli-induced peritonitis, marked by an increased recruitment of mononuclear cells, lower numbers of these cells and CCL2 levels were found in the peritoneal cavity of GILZ-deficient mice (GILZ−/−) when compared to WT. In addition, GILZ−/− showed higher bacterial loads, lower apoptosis/efferocytosis counts and a lower number of macrophages with pro-resolving phenotypes. TAT-GILZ accelerated resolution of E. coli-evoked neutrophilic inflammation, which was associated with increased peritoneal numbers of monocytes/macrophages, enhanced apoptosis/efferocytosis counts and bacterial clearance through phagocytosis. Taken together, we provided evidence that GILZ modulates macrophage migration with a regulatory phenotype, inducing bacterial clearance and accelerating the resolution of peritonitis induced by E. coli.