We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the IL-1alpha gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of IL-1alpha . Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and IL-1alpha. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and IL-1alpha induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of IL-1alpha . These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of IL-1alpha in monocytic cells via multiple signaling pathways.
Cholesterol ; Cytokines ; Inflammation ; Interleukin-1 ; Interleukin-1alpha* ; Toll-Like Receptors*

Animals ; Humans ; Interleukin-1 ; physiology ; Mice ; Pulmonary Fibrosis ; physiopathology ; Rats ; Receptors, Interleukin-1 ; physiology

Purpose: IL-1 is a multifunctional proinflammatory cytokine. As the proliferative effects of IL-6 and IL-6 receptor expressions on prostatic cancer cells in response to IL-1 have not been determined, the effects of IL-1 on prostatic cancer cell lines were investigated. Materials and Methods: PC-3 and DU-145 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum. Cell cultures were supplemented with various concentrations of IL-1 (0, 1, 10, 20 and 40ng/ml), and the MMT growth assay performed. PC-3 and DU-145 cells were treated for 2, 4, 8, 12 and 24 h both with and without IL-1. IL-6 and IL-6 receptor (IL-6R) mRNA expressions were investigated using RT-PCR, and the IL-6 levels in cultured supernatant measured by ELISA. Results: The viability of both PC-3 and DU-145 cells decreased after IL-1 treatment (10, 20 and 40ng/mul). With 40ng/ml the IL-1, IL-6 and IL-6RmRNA expressions were lower in PC-3 cells, but unchanged in DU-145 cells, whereas the IL-6 protein production was higher in both PC-3 and DU-145 cells. Conclusions: IL-1 inhibited the proliferation of both PC-3 and DU145 cells. In the PC-3 cells, IL-1 decreased the expressions of IL-6 and IL-6R mRNA, but paradoxically increased the IL-6 production. In the DU-145 cells, IL-1 treatment did not affect the IL-6 or IL-6R mRNA expressions, but the IL-6 production was increased. This discrepancy between IL-1-induced IL-6 mRNA and protein production may be mediated by modification to the protein synthesis or an increased cellular excretion.
Cell Culture Techniques ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Interleukin-1 ; Interleukin-1beta* ; Interleukin-6* ; Interleukins* ; Prostatic Neoplasms* ; Receptors, Interleukin* ; Receptors, Interleukin-6 ; RNA, Messenger

The innate immune system provides a first line of defense against invading pathogens, in which the pattern recognition receptors (PRR) recognize pathogen-associated molecular patterns (PAMP) and initiate the downstream signaling pathways to eliminate the encountered pathogens. There are two main classes of such signaling pathways: NOD-like receptor (NLR) signaling pathway and Toll-like receptor (TLR) signaling pathway. The microbial pathogens under selective pressure have evolved numerous mechanisms to avoid and/or manipulate the NLR and TLR signal transduction for survival and replication. To evade the NLR signaling pathway, pathogens interfere and/or inhibit inflammasome activation in innate immune cells by producing virulence factors or reducing PAMPs expression. The mechanisms for pathogens to evade TLR signaling pathway include: inhibition of mitogen activated protein kinases (MAPKs) cascade reaction, inhibition of NF-КB activation, and interference of down-stream signal transduction by producing Toll/interleukin-1 receptor (TIR)-containing proteins which bind directly with TLRs or adaptor proteins in the signaling pathway.
Immunity, Innate ; NLR Proteins ; immunology ; Receptors, Interleukin-1 ; metabolism ; Signal Transduction ; Toll-Like Receptors ; immunology

PURPOSE: Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. METHODS: Two large asthma family collections, the French-Canadian Saguenay-Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. RESULTS: One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). CONCLUSIONS: Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits.
Asthma ; Epidemiologic Studies ; Genetics ; Humans ; Inflammation ; Interleukin-1* ; Phenotype* ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-1 Type II*

OBJECTIVETo investigate the expression of the human interleukin-1 receptor antagonist (hIL-1ra) in the transfected chondrocytes of temporomandibular joint (TMJ).

METHODSChondrocytes of TMJ in vitro were transfected by hIL-1ra gene via cationic liposome as a medium. The stable transfected cells were selected by G418. The proliferations of the transduced cell were examined with the growth curve, cell population doubling time. The protein expressing in different periods was detected by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA).

RESULTSThe proliferation suppression of gene transfected cells fell significantly with compared to normal cells. The expression of hIL-1ra was detected in the cell plasma and the cell culture supernatant. The highest expression of IL-1ra protein was at the time of 48 hours after gene transfection. The transiently transfected cells were secreted IL-1ra protein continuously 28 days and the stably transduced cells were secreted IL-1ra protein till 72 days.

CONCLUSIONThis study showed that hIL-1ra protein expressed positively in the cell plasma and the culture supernatant after gene transfection within a certain periods.

OBJECTIVE: Schizophrenia is a disabling disorder of unknown aetiology, lacking definite diagnostic method and cure. A reliable biological marker of schizophrenia is highly demanded, for which traceable immune mediators in blood could be promising candidates. We aimed to gather the best findings of neuroinflammatory markers for first-episode psychosis (FEP). METHODS: We performed an extensive narrative review of online literature on inflammation-related markers found in human FEP patients only. RESULTS: Changes to cytokine levels have been increasingly reported in schizophrenia. The peripheral levels of IL-1 (or its receptor antagonist), soluble IL-2 receptor, IL-4, IL-6, IL-8, and TNF-α have been frequently reported as increased in FEP, in a suggestive continuum from high-risk stages for psychosis. Microglia and astrocytes establish the link between this immune signalling and the synthesis of noxious tryptophan catabolism products, that cause structural damage and directly hamper normal neurotransmission. Amongst these, only 3-hydroxykynurenine has been consistently described in the blood of FEP patients. CONCLUSION: Peripheral molecules stemming from brain inflammation might provide insightful biomarkers of schizophrenia, as early as FEP or even prodromal phases, although more time- and clinically-adjusted studies are essential for their validation.
Astrocytes ; Biomarkers ; Encephalitis ; Humans ; Interleukin-1 ; Interleukin-4 ; Interleukin-6 ; Interleukin-8 ; Metabolism ; Methods ; Microglia ; Polytetrafluoroethylene ; Psychotic Disorders ; Receptors, Interleukin-2 ; Schizophrenia ; Synaptic Transmission ; Tryptophan

BACKGROUND: The type 2 deviated immunological state is predominant in lepromatous leprosy. Erythema nodosum leprosum (ENL) is an immune-complex mediated reaction that typically occurs in lepromatous leprosy. To date, the serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-2 receptor, IL-10, IL-1beta, IL-1 receptor antagonist and monocyte chemoattractant protein-1 (MCP-1) were reported to be higher in lepromatous leprosy. TNF-alpha is also known to be higher in ENL, which is reduced after thalidomide treatment. However the serum type 2 chemokine levels in lepromatous leprosy patients have not been reported. METHODS: The serum levels of the type 2 chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and eotaxin together with IL-12 and IL-10 in the sera from leprosy patients were detected using an enzyme-linked solvent assay (ELISA) method. RESULTS: The Serum TARC, MDC, eotaxin, IL-10 and IL-12 levels in lepromatous leprosy patients were not significantly different from the normal control levels. The serum levels were not significantly different between the paucibacillary group and multibacillary group. The serum TARC or MDC levels in the ENL patients were more reduced after a treatment containing thalidomide. CONCLUSION: The type 2 chemokines are not related to the severity of lepromatous leprosy. The larger reducing effect of the TARC or MDC levels in ENL patients by a treatment containing thalidomide suggests the potential role of these chemokines in the development of ENL and the therapeutic mechanism of thalidomide.
Chemokine CCL17 ; Chemokine CCL2 ; Chemokine CCL22 ; Chemokines* ; Erythema Nodosum ; Humans ; Interleukin-1 ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Leprosy ; Leprosy, Lepromatous* ; Receptors, Interleukin-10 ; Thalidomide ; Tumor Necrosis Factor-alpha

No abstract available.
Histocompatibility Antigens Class II* ; Interleukin-1* ; Macrophages, Peritoneal* ; Phenol* ; Receptors, Fc*

No abstract available.
Histocompatibility Antigens Class II* ; Interleukin-1* ; Macrophages, Peritoneal* ; Phenol* ; Receptors, Fc*