Inflammasomes are high-molecular-weight, multiprotein complexes in cells, which are assembled after cytoplasmic nucleotide-binding oligomerization domain like receptors (NLRs) sense pathogens and danger signals. The inflammasome can activate caspase-1, and later makes the pro-IL-1β, proIL-18 precursor mature by cleavaging, thereby mediates the innate immunity. Dysregulation of inflammasomes plays an important role in the development of sepsis and other immune inflammatory diseases, thus inflammasome may be a new target for prevention and treatment of sepsis.
Caspase 1 ; immunology ; metabolism ; Humans ; Inflammasomes ; chemistry ; immunology ; metabolism ; Interleukin-18 ; immunology ; metabolism ; Interleukin-1beta ; immunology ; metabolism ; Sepsis ; immunology ; metabolism ; Signal Transduction

We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-beta)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1beta and TGF-beta. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.
Animals ; Brain/*immunology/*pathology ; Brain Injuries/immunology/*pathology/*veterinary ; Dogs ; Humans ; Interleukin-10/immunology/metabolism ; Interleukin-1beta/immunology/metabolism ; Interleukin-6/immunology/metabolism ; Transforming Growth Factor beta/immunology/metabolism ; Tumor Necrosis Factor-alpha/immunology/metabolism

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.
Apoptosis ; Burns ; immunology ; Caspase 1 ; metabolism ; Cytokines ; Humans ; Inflammasomes ; physiology ; Inflammation Mediators ; immunology ; Interleukin-18 ; immunology ; physiology ; Interleukin-1beta ; immunology ; physiology

The NLRP3 inflammasome, a protein complex belonging to the family of nucleotide-binding and oligomerization domain like receptors (NLRs), plays a vital role in the innate immune system. It promotes pro-caspase 1 cleavage into active caspase-1, which contributes to maturation and releases of IL-1β and IL-18 in response to the harmful signals and participates in the host immune response and sterile inflammation. Recently a large number of studies have shown that NLRP3 inflammasome closely relates to the pathogenesis of the vascular diseases. NLRP3 inflammasome, which involves in the sterile inflammation of the vascular wall, plays an important role in the pathogenesis of main, middle and small arteries.
Caspase 1 ; immunology ; metabolism ; Gene Expression Regulation ; genetics ; immunology ; Humans ; Inflammasomes ; immunology ; Inflammation ; complications ; genetics ; Interleukin-18 ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; NLR Family, Pyrin Domain-Containing 3 Protein ; immunology ; Signal Transduction ; genetics ; immunology ; Vascular Diseases ; etiology ; genetics ; immunology

The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.
Bacterial Infections/immunology/metabolism/pathology/prevention & control ; Carrier Proteins/*metabolism ; Caspase 1/metabolism ; Humans ; Inflammasomes/immunology/*metabolism ; Interleukin-1beta/metabolism ; Signal Transduction

OBJECTIVETo investigate the use of dendritic cells derived from mice bone marrow to evaluate the cutaneous allergic reaction induced by chemical sensitizers.

METHODSDendritic cells derived from mice bone marrow were cultured and administrated with 2, 4-dinitrochlorobenzene (DNCB), nickel sulfate (NiSO4), sodium dodecyl sulfate (SDS) and hexyl cinnamic aldehyde (HCA), respectively. Cell membrane molecule CD86 and extracellular IL-1 beta, IL-6 and IL-12 were detected after 0, 1, 6, 12, 24, 36, 48 hour's administration, respectively.

RESULTSCD86 expression reached the highest level after exposure to DNCB for 48 h, and increased by about 279% compared with the control (P < 0.05), while it was lower than that of control after administrated with NiSO4 and HCA for 1 h and 6 h, and SDS for 36 h, respectively (P < 0.05). Extracellular IL-1 beta increased greatly after exposure to NiSO4 just for 1 h, with the maximum at 48 h (298 pg/ml, P < 0.05), and after exposure to HCA for 6 h, with maximum at 48 h (84 pg/ml, P < 0.05). However, it didn't fluctuate significantly after administrated with DNCB and SDS respectively, compared with the control. Extracellular IL-6 increased significantly after exposure to NiSO4 for 1 h, with the maximum at 24 h (2152 pg/ml, P < 0.05). After exposure to HCA, extracellular IL-6 reached the maximum at 1 h (1403 pg/ml), and then it was decreased quickly, but still higher than the control (P < 0.05), while it didn't change significantly after treatment with DNCB and SDS, compared with the control (P > 0.05). Extracellular IL-12 was not detected out among all the groups.

CONCLUSIONChemical sensitizer DNCB could induce the high expression of CD86 on DC membrane, and NiSO4 and HCA could induce DC to release IL-1 beta and IL-6. However, the irritant SDS had no such effect.

Animals ; B7-2 Antigen ; metabolism ; Cells, Cultured ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Dinitrochlorobenzene ; pharmacology ; Interleukin-12 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred C57BL ; Nickel ; pharmacology ; Sodium Dodecyl Sulfate ; pharmacology

OBJECTIVETo explore the effects of acrylonitrile on T lymphocyte subsets, expression of toll-like receptor 4 and related cytokines in rats.

METHODSSixty-four Sprague-Dawley rats were randomly divided into 4 female groups and 4 male groups, and there were 8 rats in each group. Rats in each group were respectively given a single dose of 0, 5, 10 and 20 mg/kg acrylonitrile by gavage, once a day, 5 days a week, for 13 weeks. Blood and spleen T lymphocyte subsets was detected by flow cytometry, the mRNA expression of TLR4, IL-1β and TNF-α was analyzed by real-time quantitative PCR, the protein expression of TLR4 was evaluated by Western blot.

RESULTSCompared with control group, the percentages of blood CD3, CD4 T cells in 20 mg/kg female group and CD4/CD8 ratio in 5, 10 and 20 mg/kg female groups was significantly decreased, CD8 T cells in 20 mg/kg group was significantly increased (P < 0.05 or P < 0.01), blood CD3 T cells in 5 mg/kg male group, CD4 T cells and CD4/CD8 ratio in 20 mg/kg male groups were lower than that of control group, CD8 T cells in 20 mg/kg make group was significantly in oreased (P < 0.05 or P < 0.01). Spleen CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in 20 mg/kg female group decreased significantly, CD8 T cells in 20 mg/kg male group was significantly increased (P < 0.05 or P < 0.01), spleen CD3, CD4, CD8 T cells in 20 mg/kg male group and CD4/CD8 ratio in 10, 20 mg/kg male groups was also significantly decreased, CD3 T cells in 20 mg/kg and CD8 T cells in 10, 20 mg/kg male groups were significantly increased (P < 0.05 or P < 0.01) (TLR4 mRNA was lower expressed in 5, 10 and 20 mg/kg male groups and 10 mg/kg female group (P < 0.05 or P < 0.01), and TLR4 protein in 5 mg/kg female group and 20 mg/kg male group was significantly lower than control group (P < 0.05). The expression level of IL-1β mRNA was significantly decreased in 5, 10 and 20 mg/kg female group and 5, 10 mg/kg male group (P < 0.05 or P < 0.01), TNF-α mRNA was lower expressed in 10, 20 mg/kg female groups and 5, 10 mg/kg male groups (P < 0.01).

CONCLUSIONAcrylonitrile may lead to the changes of CD3, CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in rat blood and spleen, and also significantly effected the expression level of TLR4 mRNA and protein together with the secretion of IL-1β, TNF-α. This may cause effects on the cellular immune function.

Acrylonitrile ; toxicity ; Animals ; Female ; Interleukin-1beta ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; T-Lymphocyte Subsets ; drug effects ; immunology ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the effects of immunoglobulin on the neuronal expression of IL-1beta and IL-1ra and the neuronal death at hippocampus in rats with convulsion induced by pentylenetetrazol.

METHODSThe epilepsy model was established by injecting intraperitoneally pentylenetetrazol (PTZ) into Wistar rats. Forty-five rats were randomly divided into three groups, normal control group, PTZ plus intravenous immunoglobulin (PTZ-IVIG); PTZ plus normal saline (PTZ-NS). Neuronal death was assessed by light microscopy with the hematoxylin-eosin (HE) staining and with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). IL-1beta and IL-1ra expressions were examined by histochemistry.

RESULTSThe ratio of IL-1beta/IL-1ra at hippocampal CA(1) region in PTZ-IVIG group (0.5 +/- 0.1) was significantly lower than that in PTZ-NS group (1.9 +/- 0.5, t = 12.9, P < 0.05). Apoptotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group, compared to PTZ-NS group (t = 27.1, P < 0.05). The numbers of positive cells were 16.4 +/- 3.3/1000 microm(2) in the former and 41.7 +/- 3.5/1000 microm(2) in the latter. Necrotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group (19.0 +/- 2.6/1000 microm(2)), compared to PTZ-NS group (42.3 +/- 4.9/1000 microm(2), t = 20.9, P < 0.05).

CONCLUSIONImmunoglobulin could inhibit neuronal death induced by convulsion and its possible mechanism might be the regulation of IL-1 system in neurons.

Animals ; Apoptosis ; Hippocampus ; drug effects ; immunology ; metabolism ; Immunoglobulins, Intravenous ; pharmacology ; Interleukin 1 Receptor Antagonist Protein ; metabolism ; Interleukin-1beta ; metabolism ; Neurons ; drug effects ; Pentylenetetrazole ; adverse effects ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; immunology ; metabolism

BACKGROUNDPediatric patients are susceptible to lung injury. Acute lung injury (ALI) in children often results in a high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA).

METHODSTwelve Chinese immature piglets were induced to develop ALI by oleic acid. The animals were randomly assigned to two groups (n = 6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.

RESULTSCompared with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha both in plasma and tissue concentrations compared with MV group (P < 0.05).

CONCLUSIONSPartial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

Animals ; Fluorocarbons ; therapeutic use ; Hemodynamics ; drug effects ; Inflammation ; chemically induced ; therapy ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Liquid Ventilation ; methods ; Lung Injury ; immunology ; therapy ; Oleic Acid ; toxicity ; Random Allocation ; Respiration, Artificial ; Swine ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. CONCLUSION Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-1beta ; metabolism ; Pharyngitis ; drug therapy ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism