scholarly journals Mechanism of the fungal-like particles in the inhibition of adipogenesis in 3T3-L1 adipocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chanawee Jakkawanpitak ◽  
Masashi Inafuku ◽  
Hirosuke Oku ◽  
Nongporn Hutadilok-Towatana ◽  
Ruthaiwan Bunkrongcheap ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lipid Accumulation ◽  
Early Stage ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Lectin Domain ◽  
Cycle Arrest ◽  
Toll Like Receptor 2 ◽  
Amp Activated Protein Kinase

AbstractThe dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health. Previously, we established laminarin-coated beads or LCB as an inflammatory elicitor for adipocytes. However, it was not clear whether LCB inhibits lipid accumulation in adipocytes. Here, we show that LCB acts in the early stage of adipogenesis through both interleukin-1 receptor-associated kinases (IRAK) and spleen tyrosine kinase (SYK) pathways, resulting in the activation of the AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB) complexes, which subsequently cause cell cycle arrest, downregulation of the key transcription factors and enzymes responsible for adipogenesis, inhibition of adipogenesis, and stimulation of an inflammatory response. While LCB could effectively block lipid accumulation during the early stage of adipogenesis, it could stimulate an inflammatory response at any stage of differentiation. Additionally, our results raise a possibility that toll-like receptor 2 (TLR2) and C-type lectin domain family 7 member A (CLEC7A/Dectin-1) might be potential β-glucan receptors on the fat cells. Together, we present the mechanism of LCB, as fungal-like particles, that elicits an inflammatory response and inhibits adipogenesis at the early stage of differentiation.

scholarly journals Serum amyloid A induces interleukin-6 in dermal fibroblasts via Toll-like receptor 2, interleukin-1 receptor-associated kinase 4 and nuclear factor-κB

Immunology ◽  
2014 ◽  
Vol 143 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Steven O'Reilly ◽  
Rachel Cant ◽  
Marzena Ciechomska ◽  
James Finnigan ◽  
Fiona Oakley ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Serum Amyloid A ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Dermal Fibroblasts ◽  
Serum Amyloid ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Amyloid A ◽  
Toll Like Receptor 2

scholarly journals Mechanism of the Fungal-like Particles in the Inhibition of Adipogenesis in 3t3-l1 Adipocytes

2021 ◽  
Author(s):  
Chanawee Jakkawanpitak ◽  
Masashi Inafuku ◽  
Hirosuke Oku ◽  
Nongporn Hutadilok-Towatana ◽  
Ruthaiwan Bunkrongcheap ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Adipose Tissue ◽  
Transcription Factors ◽  
Inflammatory Response ◽  
Human Health ◽  
Lipid Accumulation ◽  
Early Stage ◽  
Cycle Arrest ◽  
Stimulation Of

Abstract The dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health. Previously, we established laminarin-coated beads or LCB as an inflammatory elicitor for adipocytes. However, it was not clear whether LCB inhibits lipid accumulation in adipocytes. Here, we show that LCB acts in the early stage of adipogenesis through both IRAK and SYK pathways, resulting in the activation of the AMPK and NF-kB complexes, which subsequently cause cell cycle arrest, suppression of C/EBPb, PPARg, C/EBPa, FAS, FABP4, and ACC proteins, downregulation of other transcription factors and enzymes, such as Pparg, C/ebpa, Srebp-1, Lpl, and Fas gene expression, inhibition of adipogenesis, and stimulation of an inflammatory response. Unlike the inhibition of adipogenesis, LCB could stimulate an inflammatory response at any stage of differentiation. In addition, we find that Tlr2 and Clec7a/Dectin-1 but not Tlr4 and Cd36 gene expression are upregulated upon the treatment with LCB, suggesting that TLR2 and CLEC7A/Dectin-1 might be the b-glucan receptors for the cells. Together, we present the mechanism of LCB, as fungal-like particles, that elicit an inflammatory response and inhibit adipogenesis at the early stage of differentiation.

scholarly journals CD4+CD25+Foxp3+ regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052098094
Author(s):  
Shuang Qin ◽  
Li Li ◽  
Jia Liu ◽  
Jinrui Zhang ◽  
Qing Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Tlr4 Antagonist

Objective The present study aimed to evaluate the effects of cluster of differentiation (CD)4+CD25+ forkhead box p3 (Foxp3)+ regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. Methods The proportion of CD4+CD25+Foxp3+ Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. Results The proportion of CD4+CD25+Foxp3+ Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4+CD25+Foxp3+ Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. Conclusions These data suggest that CD4+CD25+Foxp3+ Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.

scholarly journals Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2

2001 ◽  
Vol 69 (4) ◽  
pp. 2230-2236 ◽  
Author(s):  
Robin R. Ingalls ◽  
Egil Lien ◽  
Douglas T. Golenbock
Keyword(s):  
Cell Wall ◽  
Inflammatory Response ◽  
Neisseria Meningitidis ◽  
Parental Strain ◽  
Host Responses ◽  
Deficient Mutant ◽  
Toll Like Receptor ◽  
Gram Negative ◽  
Negative Cell ◽  
Toll Like Receptor 2

ABSTRACT The recent isolation of a lipopolysaccharide (LPS)-deficient mutant of Neisseria meningitidis has allowed us to explore the roles of other gram-negative cell wall components in the host response to infection. The experiments in this study were designed to examine the ability of this mutant strain to activate cells. Although it was clearly less potent than the parental strain, we found the LPS-deficient mutant to be a capable inducer of the inflammatory response in monocytic cells, inducing a response similar to that seen with Staphylococcus aureus. Cellular activation by the LPS mutant was related to expression of CD14, a high-affinity receptor for LPS and other microbial products, as well as Toll-like receptor 2, a member of the Toll family of receptors recently implicated in host responses to gram-positive bacteria. In contrast to the parental strain, the synthetic LPS antagonist E5564 did not inhibit the LPS-deficient mutant. We conclude that even in the absence of LPS, the gram-negative cell wall remains a potent inflammatory stimulant, utilizing signaling pathways independent of those involved in LPS signaling.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

Insights from vaccinia virus into Toll-like receptor signalling proteins and their regulation by ubiquitin: role of IRAK-2

2008 ◽  
Vol 36 (3) ◽  
pp. 449-452 ◽  
Author(s):  
Andrew G. Bowie
Keyword(s):  
Vaccinia Virus ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Tumour Necrosis Factor Receptor ◽  
Relative Role ◽  
Toll Like Receptor ◽  
Turn On ◽  
Receptor Signalling ◽  
Necrosis Factor

TLRs (Toll-like receptors) are an important class of pathogen-sensing proteins, which signal the presence of a pathogen by activating transcription factors, such as NF-κB (nuclear factor κB). The TLR pathway to NF-κB activation involves multiple phosphorylation and ubiquitination events. Notably, TRAF-6 [TNF (tumour necrosis factor)-receptor-associated factor-6] Lys63 polyubiquitination is a critical step in the formation of signalling complexes, which turn on NF-κB. Here, the relative role of different IRAKs [IL-1 (interleukin 1)-receptor-associated kinases] in NF-κB activation is discussed. Further, I demonstrate how understanding one molecular mechanism whereby vaccinia virus inhibits NF-κB activation has led to a revealing of a key role for IRAK-2 in TRAF-6-mediated NF-κB activation.

scholarly journals Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mingxu Xia ◽  
Qiuchen Zhao ◽  
He Zhang ◽  
Yanting Chen ◽  
Zengqiang Yuan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Treated Group ◽  
Toll Like Receptor ◽  
Primary Microglia ◽  
Protein Mass ◽  
Protein Mass Spectrometry ◽  
Receptor Signaling Pathway ◽  
Toll Like Receptor 2 ◽  
Protein Alterations

HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway. In this regard, we selected Toll-like receptor 2 (TLR2), TLR3, TLR6, MAPK p38, CD36, and spleen tyrosine kinase (SYK) for further validation and found that they were all significantly upregulated after LPS stimulation and downregulated in the presence of RGFP966. Additionally, RGFP966 inhibited supernatant tumor necrosis factor (TNF)-α and Interleukin 6 (IL-6) concentrations. Activation of STAT3 and STAT5 was partially blocked by RGFP966 at 2 h after LPS-stimulation. The fluorescence intensity of CD16/32 was significantly decreased in LPS + RGFP966-treated group. In conclusion, our data provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways.

scholarly journals Interleukin-1 Receptor but Not Toll-Like Receptor 2 Is Essential for MyD88-Dependent Th17 Immunity to Coccidioides Infection

2014 ◽  
Vol 82 (5) ◽  
pp. 2106-2114 ◽  
Author(s):  
Chiung-Yu Hung ◽  
María del Pilar Jiménez-Alzate ◽  
Angel Gonzalez ◽  
Marcel Wüthrich ◽  
Bruce S. Klein ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Cell Activation ◽  
Pulmonary Infection ◽  
Interleukin 1 ◽  
Signal Pathways ◽  
Toll Like Receptor ◽  
Content Type ◽  
Toll Like Receptor 2

ABSTRACTInterleukin-17A (IL-17A)-producing CD4+T helper (Th17) cells have been shown to be essential for defense against pulmonary infection withCoccidioidesspecies. However, we have just begun to identify the required pattern recognition receptors and understand the signal pathways that lead to Th17 cell activation after fungal infection. We previously reported thatCard9−/−mice vaccinated with formalin-killed spherules failed to acquire resistance toCoccidioidesinfection. Here, we report that bothMyD88−/−andCard9−/−mice immunized with a live, attenuated vaccine also fail to acquire protective immunity to this respiratory disease. LikeCard9−/−mice, vaccinatedMyD88−/−mice revealed a significant reduction in numbers of both Th17 and Th1 cells in their lungs afterCoccidioidesinfection. Both Toll-like receptor 2 (TLR2) and IL-1 receptor type 1 (IL-1r1) upstream of MyD88 have been implicated in Th17 cell differentiation. Surprisingly, vaccinatedTLR2−/−and wild-type (WT) mice showed similar outcomes after pulmonary infection withCoccidioides, while vaccinatedIL-1r1−/−mice revealed a significant reduction in the number of Th17 cells in their infected lungs compared to WT mice. Thus, activation of both IL-1r1/MyD88- and Card9-mediated Th17 immunity is essential for protection againstCoccidioidesinfection. Our data also reveal that the numbers of Th17 cells were reduced inIL-1r1−/−mice to a lesser extent than inMyD88−/−mice, raising the possibility that other TLRs are involved in MyD88-dependent Th17 immunity to coccidioidomycosis. An antimicrobial action of Th17 cells is to promote early recruitment of neutrophils to infection sites. Our data revealed that neutrophils are required for vaccine immunity to this respiratory disease.

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