Dual dose-related effects evoked by CCL4 on thermal nociception after gene delivery or exogenous administration in mice.

As recently described, the administration of extremely low doses (pg/kg) of CCL4 (Macrophage inflammatory protein 1β, MIP-1β) can induce antinociceptive effects in mice (García-Domínguez et al., 2019b). We describe here that hydrodynamic delivery of a plasmid containing CCL4 cDNA provokes a biphasic response consisting in an initial thermal hyperalgesic reaction for 8 days followed by analgesia at days 10-12, being both responses blocked after the administration of the CCR5 antagonist DAPTA.

The Systemic Administration of the Chemokine CCL1 Evokes Thermal Analgesia in Mice Through the Activation of the Endocannabinoid System.

Apart from its involvement in immune functions, the chemokine CCL1 can participate in the modulation of nociceptive processing. Previous studies have demonstrated the hypernociceptive effect produced by CCL1 in the spinal cord, but its possible action on peripheral nociception has not yet been characterized. We describe here that the subcutaneous administration of CCL1 (1-10 µg/kg) produces dose-dependent and long-lasting increases in thermal withdrawal latencies measured by the unilateral hot plate test in mice.

Matrix metalloproteinase-14 triggers an anti-inflammatory proteolytic cascade in endotoxemia.

Unlabelled: ᅟ: Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 mice were challenged with lipopolysaccharide.

Loss of MT1-MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid.

MT1-MMP (MMP14) is a collagenolytic enzyme located at the cell surface and implicated in extracellular matrix (ECM) remodeling. Mmp14(-/-) mice present dwarfism, bone abnormalities, and premature death. We demonstrate herein that the loss of MT1-MMP also causes cardiac defects and severe metabolic changes, and alters the cytoskeleton and the nuclear lamina structure.

Defective autophagy impairs ATF3 activity and worsens lung injury during endotoxemia.

Unlabelled: Autophagy has emerged as a key regulator of the inflammatory response. To examine the role of autophagy in the development of organ dysfunction during endotoxemia, wild-type and autophagy-deficient (Atg4b-null) mice were challenged with lipopolysaccharide. Animals lacking Atg4b showed increased mortality after endotoxemia.

Clinical significance of toll-like receptor 3, 4, and 9 in gastric cancer.

Toll-like receptors (TLRs) have raised an extraordinary interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, TLR4, and TLR9 in gastric cancer.

Mechanical ventilation triggers hippocampal apoptosis by vagal and dopaminergic pathways.

Rationale: Critically ill patients frequently develop neuropsychological disturbances including acute delirium or memory impairment. The need for mechanical ventilation is a risk factor for these adverse events, but a mechanism that links lung stretch and brain injury has not been identified.

Objectives: To identify the mechanisms that lead to brain dysfunction during mechanical ventilation.

ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy.

Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury.

Background: Mechanical ventilation can promote lung injury by triggering a pro-inflammatory response. Macrolides may exert some immunomodulatory effects and have shown significant benefits over other antibiotics in ventilated patients. We hypothesized that macrolides could decrease ventilator-induced lung injury.

Impairment of autophagy decreases ventilator-induced lung injury by blockade of the NF-κB pathway.

Excessive lung stretch triggers lung inflammation by activation of the NF-κB pathway. This route can be modulated by autophagy, an intracellular proteolytic system. Our objective was to study the impact of the absence of autophagy in a model of ventilator-induced lung injury.

MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia.

Matrix metalloproteinase-8, released mainly from neutrophils, is a critical regulator of the inflammatory response by its ability to cleave multiple mediators. Herein, we report the results of a model of endotoxemia after intraperitoneal LPS injection in mice lacking MMP-8 and their wildtype counterparts. Control, saline-treated animals showed no differences between genotypes.

Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence.

Background: Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, and 9 in prostate cancer.